melphalan and Cell-Transformation--Neoplastic

Topics: Antineoplastic Agents, Alkylating; Cell Transformation, Neoplastic; Child; Follow-Up Studies; Humans; Infant; Infusions, Intra-Arterial; Male; Melphalan; Ophthalmoscopy; Retinal Neoplasms; Retinoblastoma

Cell transformation assays (CTAs) are currently regarded as the only possible in vitro alternative to animal testing for carcinogenesis studies. CTAs have been proposed as screening tests for the carcinogenic potential of compounds that have no evidence of genotoxicity but present structural alerts for carcinogenicity. We have extensively used the BALB/c 3T3 model based on the A31 cell clone to test single chemicals, complex mixtures and environmental pollutants. In the prevalidation study carried out by ECVAM, the improved protocol is based on BALB/c 3T3 A31-1-1 cells, a clone derived by A31 cells, that is very sensitive to PAH-induced transformation. The present study was performed in the aim to compare the results obtained with the two different clones exposed to different classes of carcinogens. Cells were treated with PAHs (3-methylcholanthrene, benzo(a)pyrene), alkylating agents (melphalan) and aloethanes (1,2-dibromoethane). The induction of cytotoxicity and the onset of chemically transformed foci were evaluated by two experimental protocols, differing for cell seeding density and chemical treatment duration. The A31-1-1 cells showed higher inherent transformation rate after PAHs treatment, but they were insensitive to 1,2-dibromoethane at concentrations that usually induced transformation in A31 cells. As 1,2-dibromoethane is bioactivated to reactive forms able to bind DNA mainly through the conjugation with intracellular glutathione, these results suggested a reduced activity of phase-2 enzymes involved in glutathione conjugation in A31-1-1 cells. Our results give evidence that inherent metabolic capacity of cells may play a critical role in in vitro cell transformation, cautioning against possible misclassification of chemicals.

Topics: Animals; Antineoplastic Agents, Alkylating; BALB 3T3 Cells; Carcinogenicity Tests; Carcinogens; Cell Transformation, Neoplastic; Clone Cells; Ethylene Dibromide; Melphalan; Mice; Polycyclic Aromatic Hydrocarbons

Leukemic transformation (LT) from myelofibrosis has a very poor prognosis with the current treatment strategies. We hypothesized that allogeneic stem cell transplantation (ASCT) can improve outcomes for patients with LT, and reviewed 55 consecutive patients that were treated for myelofibrosis with ASCT at our institution. Fourteen patients (25%) were identified to have LT. Thirteen of these patients received induction chemotherapy and 6 achieved remission at the time of transplant. Conditioning regimen was melphalan (Mel)-based in 9 patients. All patients engrafted and achieved remission after transplant, whereas 4 subsequently relapsed. After a median follow-up of 31 months, 6 patients (49%) survived long term. Although limited by a small number of patients, this study suggests that patients with myelofibrosis and LT may achieve long-term remission after induction chemotherapy and ASCT.

Topics: Aged; Cell Transformation, Neoplastic; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Melphalan; Middle Aged; Primary Myelofibrosis; Prognosis; Transplantation Conditioning; Treatment Outcome

The prediction of the carcinogenic risk for humans is mostly based on animal experiments. For the last 20 years, however, the scientific community has paid great attention to alternative strategies in compliance with common moral and ethical values. The new European chemical regulation REACH (Reg. EC 1907/2006) requires the performance of new studies in vertebrates only as a last resort. REACH asks for the development of validated in vitro protocols that can replace, in the medium to the long term, animal bioassays. An in vitro cell transformation assay (CTA) is proposed as an alternative to in vivo carcinogenicity testing. This assay is reported in the list of accepted methods for REACH (Reg. EC 440/2008). The BALB/c 3T3 model represents one of the most well-known CTAs and is regarded as a useful tool to screen single chemicals or complex mixtures for carcinogenicity prediction. In this study we used a modified protocol to highlight the transforming potential of three single compounds, ethinylestradiol (EE), azathioprine (AZA-T), melphalan, and two polychlorinated biphenyls (PCBs) mixtures, which are known or suspected to be human carcinogens. We also evaluated the activity of the antioxidant alpha-lipoic acid (ALA), a promising tumor chemopreventive. A significant increase in transformation frequency was observed when the BALB/c 3T3 cells were exposed to EE, AZA-T or melphalan as well as after PCBs treatment. On the contrary, ALA did not induce any increase of foci occurrence. Our results confirm the suitability of the improved protocol to discriminate carcinogenic compounds and support the use of BALB/c 3T3 cell transformation assay as a possible alternative to predict carcinogenic risk to humans.

Topics: Animals; Azathioprine; BALB 3T3 Cells; Carcinogenicity Tests; Carcinogens; Cell Transformation, Neoplastic; Environmental Pollutants; Ethinyl Estradiol; Melphalan; Mice; Polychlorinated Biphenyls

The p53 tumour suppressor gene is frequently mutated in human tumours and different tumour-derived mutations have varying effects on cells. The effect of a novel tumour-derived p53 mutation and two recently described mutations from South African breast cancer patients on the growth rate, colony formation, cell cycle arrest after irradiation and response to chemotherapeutic drugs was investigated. None of the p53 mutations had any significant effect on the inherent growth rate of the cells; however, contact inhibition of growth in two of the mutants was lost. These same two mutants formed colonies in soft agar, whereas the third mutant did not. All three of the mutants failed to show a G(1) cell cycle arrest after exposure to 7 Gy of [(60)Co] radiation, albeit to different degrees. Cells expressing the p53 mutants were either more sensitive to cisplatin and melphalan or more resistant than the untransfected cells, depending on the mutation. However, there was no difference in response to daunorubicin treatment. These results demonstrate that different p53 mutations exert varying biological effects on normal cells, with some altering checkpoint activation more effectively than others. The data also suggest that the nature of the p53 mutation influences the sensitivity to cytostatic drugs.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Blotting, Western; Cell Cycle; Cell Division; Cell Survival; Cell Transformation, Neoplastic; Cisplatin; Daunorubicin; DNA, Complementary; Immunohistochemistry; Kinetics; Melphalan; Mice; Models, Molecular; Mutation; NIH 3T3 Cells; Protein Conformation; Transfection; Tumor Suppressor Protein p53

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cell Transformation, Neoplastic; Cyclophosphamide; Cytarabine; Doxorubicin; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocyte Transfusion; Melphalan; Podophyllotoxin; Prednisone; Remission Induction; Rituximab; Time Factors; Vincristine

A 52-year-old woman complained of lower back pain and gluteal pain in April 1997, and was found to have anemia, hypercalcemia and renal disorder. In September of the same year, she was diagnosed as having IgA-lambda myeloma (stage IIIA). VMMD-IFN therapy was started in November, 1997, and this resulted in improvement of the M-protein level, and relief of the pain in the lower back and gluteal region. A second course of VMMD-IFN therapy was also effective. In April 1998, however, the back pain worsened, and in July the patient suffered a fall and fractured her left femur. Upon readmission to our hospital, the level of M-protein was lower, and high fever, hypercalcemia, renal disorder, elevation of the LDH level, anemia and thrombocytopenia were observed. Bone marrow examination revealed 30% atypical large-sized CD19-, CD38+, CD56+ myeloma cells and chromosomal abnormalities. Although the symptoms were improved temporarily after a third course of VMMD therapy, disease aggravation occurred again, and extramedullary masses appeared on the head, face and pelvis. VAD therapy was performed without effect, and the patient died about 2 months after recurrence. This was a comparatively rare case of fulminant multiple myeloma occurring in the terminal stage.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Transformation, Neoplastic; Dexamethasone; Female; Humans; Immunoglobulin A; Immunoglobulin lambda-Chains; Interferon-alpha; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Vincristine

Many tumor types have p53 and/or RB mutations, and it is unclear what role the mutations of these tumor suppressor genes have on the efficacy of chemotherapeutic agents. The effect of p53 and RB inactivation on sensitivity to chemotherapeutic drugs was examined using a model system in which p53 or RB was inactivated in normal human foreskin fibroblasts (HFFs) by acute expression of human papillomavirus (HPV) 16E6 or 16E7. Cytotoxicity assays showed that HFFs expressing HPV 16E6 were 6- to 9-fold more sensitive to the DNA crosslinkers cisplatin and carboplatin and 7.8- to 11.5-fold more sensitive to the tubulin polymerizing agent paclitaxel than were LXSN-expressing cells. Analysis of mouse embryonal fibroblasts lacking p53 (p53-/-) compared with mouse embryonal fibroblasts homozygous (p53+/+) and heterozygous (p53+/-) for wild-type p53 confirmed the role of p53 in the enhanced sensitivity to cisplatin. Treatment with the alkylating agents melphalan and nitrogen mustard resulted in 3.8- to 7.3-fold greater sensitivity in HPV 16E6- or 16E7-expressing cells compared with LXSN-expressing cells. Enhanced sensitivity to cisplatin in cells lacking p53 function was explored by examination of its effects on cell cycle progression after exposure. When treated with cisplatin, HFFs expressing 16E6 showed delayed progression through S phase relative to HFFs expressing LXSN. The delay in S phase progression was coincident with the induction of p53 protein levels in LXSN-containing HFFs, suggesting a role for p53 in DNA repair of cisplatin-induced damage. These results indicate that the inactivation of p53 in the absence of other genetic alterations leads to enhanced sensitivity to multiple chemotherapeutic agents rather than to increased resistance.

Topics: Animals; Antineoplastic Agents; Aphidicolin; Carboplatin; Cell Cycle; Cell Line, Transformed; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; Cisplatin; Embryo, Mammalian; Fibroblasts; Genes, p53; Genes, Retinoblastoma; Heterozygote; Homozygote; Humans; Infant, Newborn; Kinetics; Male; Mechlorethamine; Melphalan; Mice; Oncogene Proteins, Viral; Paclitaxel; Papillomaviridae; Papillomavirus E7 Proteins; Repressor Proteins; Skin; Time Factors

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Topics: Acute Disease; Anemia, Refractory, with Excess of Blasts; Busulfan; Cell Transformation, Neoplastic; Chlorambucil; Cohort Studies; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Hydroxyurea; Incidence; Interferon-alpha; Leukemia; Leukemia, Radiation-Induced; Male; Melphalan; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Preleukemia; Primary Myelofibrosis; Retrospective Studies; Ribonucleotide Reductases; Risk; Thrombocythemia, Essential

The therapeutic potential of six cytokines, eight cytotoxic drugs and two effector cell populations for the treatment of multiple myeloma was assessed in vitro using the 5T33 murine myeloma model. The efficacy of combination IFN-alpha and melphalan therapy was also evaluated in vitro and in vivo. Of the cytokines tested in vitro using the MTT assay, only IFN-alpha demonstrated significant inhibition of myeloma cell growth at non-toxic concentrations (ED50 = 1508.3 +/- 181.3 U/mL and 2617.9 +/- 334.0 U/mL for murine IFN-alpha [mIFN-alpha] and human IFN-alpha hybrid B/D [hIFN-alpha B/D], respectively). The ED50 for the eight cytotoxic drugs tested ranged from 2.3 x 10(-9) to 4.3 x 10(-13) mol/L and all were within the therapeutic range for humans. Combination hIFN-alpha B/D and melphalan were found to be additive in their inhibitory effects on myeloma cell growth in vitro and this finding was confirmed in vivo in C57BL/KaLwRij mice bearing disseminated 5T33 myeloma. Control animals demonstrated a median survival duration of 25.3 days whereas hIFN-alpha B/D or melphalan treatment alone increased survival to 30.5 and 33.3 days, respectively (P < 0.001). Combination IFN-alpha/melphalan therapy increased median survival duration to 38.5 days (P < 0.001) which was also significantly greater than that obtained with single agent therapy (P < 0.01). The murine myeloma cells were found to be resistant to NK cell lysis but susceptible to lysis by LAK cells (49.3 +/- 6.3% lysis at an effector to target ratio of 100:1).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antineoplastic Agents; Cell Division; Cell Transformation, Neoplastic; Combined Modality Therapy; Cytokines; Cytotoxicity, Immunologic; Female; Humans; Interferon-alpha; Interleukins; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Male; Melphalan; Mice; Mice, Inbred C57BL; Multiple Myeloma; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

The clinical and pathologic findings in a 53-year-old woman who developed a uterine adenosarcoma following an adenomyoma are described. During the interval between the diagnosis of adenomyoma and the subsequent diagnosis of adenosarcoma, the patient developed breast carcinoma and received adjuvant chemotherapy that included tamoxifen. The possible stimulatory effects of this drug upon the patient's pre-existing adenomyoma are discussed in view of reports of tamoxifen-associated endometrial carcinoma and uterine sarcomas developing in the setting of estrogen excess.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cell Transformation, Neoplastic; Combined Modality Therapy; Doxorubicin; Endometriosis; Female; Fluorouracil; Humans; Melphalan; Menopause; Middle Aged; Tamoxifen; Uterine Neoplasms; Wilms Tumor

The influences on host immunosuppression by treatment with cyclophosphamide (200 mg/kg), steroid (prednisolone, 12.0 mg/kg for seven doses or 235 mg/kg for one dose), and adult thymectomy on tumor growth were compared. Treatment with cyclophosphamide 24 hr prior to MOPC 104E tumor transplantation produced the greatest facilitation of tumor growth. The role of prednisolone in rendering the MOPC 104E cells more vulnerable to conventional chemotherapy was also investigated. The combination of prednisolone with melphalan added measurably to the cytotoxicity of the treatment and increased the percentage of disease-free survivors. The observed effects of prednisolone might have been due to the increase in the cycling of myeloma cells directly, or the drug may have facilitated growth of the myeloma by blocking host expansion of T-cell immunity. Alterations of the host by adult thymectomy and immunosuppression with cyclophosphamide or prednisolone led to growth facilitation of myeloma. The limited studies reported here point out the usefulness of facilitation of tumor growth to accomplish increased neoplastic cell kill and increased percentage of disease-free survivors.

Topics: Animals; Cell Cycle; Cell Line; Cell Transformation, Neoplastic; Cyclophosphamide; Female; Immunosuppression Therapy; Melphalan; Mice; Mice, Inbred BALB C; Multiple Myeloma; Prednisolone

Topics: Animals; Carmustine; Cell Transformation, Neoplastic; Clone Cells; Colony-Forming Units Assay; DNA; Doxorubicin; Drug Resistance; Humans; Hypergammaglobulinemia; Interferons; Melphalan; Mice; Mice, Inbred BALB C; Multiple Myeloma; Vinblastine; Waldenstrom Macroglobulinemia

An established line of mouse fibroblasts (10T1/2 cells) cultured in vitro was used to compare the incidence of oncogenic transformation produced by x rays, the hypoxic cell radiosensitizer misonidazole, and a range of commonly used chemotherapy agents. A 3-day exposure to misonidazole at a concentration obtainable during treatment produced an incidence of transformation similar to that of about 50 rad. When chemotherapy agents were tested at concentrations comparable to those used clinically and matched to produce similar cell killing, the incidence of transformation varied widely: some agents, such as vincristine, did not produce transformation at a level detectable above background, while others, such as cis-platinum, appear to be potent carcinogens and produce transformation at a rate orders of magnitude higher than that achieved with x rays.

Topics: Animals; Antineoplastic Agents; Azacitidine; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; Cisplatin; Doxorubicin; Fibroblasts; In Vitro Techniques; Melphalan; Mice; Misonidazole; Nitroimidazoles; Radiation, Ionizing; Vincristine; X-Rays

The kinetics of myeloma cells at diagnosis and during complete remission were compared on 4 IgG K patients. We were able to study experimentally the kinetics of the minimal tumor mass because we prepared anti-idiotypic sera specifically directed against the hypervariable region of the M protein. We have shown that the residual myeloma cell labelling index during remission is usually lower than that observable on diagnosis. This finding conflicts with the current opinion on minimal tumor mass kinetics. Therefore, it is suggested that a new therapeutic strategy should be adopted in the complete remission phase.

Topics: Blood Proteins; Bone Marrow; Cell Transformation, Neoplastic; Fluorescent Antibody Technique; Humans; Immunoglobulins; Kinetics; Melphalan; Multiple Myeloma

In multiple myeloma, tumor cell mass and labeling index correlate with subsequent survival duration, but do not predict for response to treatment. In the present study was have autoradiographically measured the incorporation of 3H-thymidine as determined by the number of grains over the myeloma nuclei in bone marrow aspiration samples. In 33/37 patients with less than 50% tumor regression or progressive disease, the pretreatment grain count was greater than or equal to 20/myeloma nucleus. Conversely, values of less than 20 were found in 27/29 patients who had greater than or equal to 50% cell mass reduction. Survival duration was significantly better than (p less than 0.001) in patients with grain counts less than 20. Sixty percent of the patients with both a low labeling index (less than or equal to 3%) and grain count (less than 20) were alive at 48 mo, whereas 15/17 patients with a high labeling index and grain count had a median survival of less than 6 mo. In a subset of 22 patients, there as a significant correlation between in vitro resistance to melphalan, adriamycin, and vincristine as tested in the myeloma stem cell colony assay system and a grain count of greater than 20. We can only speculate as to the reasons for the increased 3H-thymidine uptake by myeloma cells resistant to treatment, however, it could be associated with accumulation of excess DNA and /or increased unscheduled DNA synthesis following injury from alkylating agents.

Topics: Carmustine; Cell Nucleus; Cell Transformation, Neoplastic; Doxorubicin; Drug Resistance; Drug Therapy, Combination; Humans; Melphalan; Multiple Myeloma; Thymidine; Vincristine

A patient with multiple myeloma developed periodic blood neutropenia (periodicity of 15-25 days) after 3 yr of intermittent treatment with cytotoxic agents. Peaks of serum colony-stimulating activity (CSA) level coincided with valleys of blood neutrophils. Fraction of marrow neutrophils in the multiplicative pool was high during blood neutrophil valleys and low during neutrophil peaks. In contrast, the maturation storage pool exhibited the reverse pattern. An increased fraction of marrow neutrophilic cells in the multiplicative pool was in active proliferation during a blood neutrophil valley and a decreased fraction during a blood neutrophil peak. These findings suggest that the marrow granulopoiesis was regulated through CSA. The defect causing the periodicity was probably related to the reduced number of neutrophils in the marrow maturation storage pool, which in turn may be related to a reduced and/or defective granulocytic stem cell pool size consequent to the long-term administration of cytotoxic drugs and/or infiltration of the marrow by myeloma cells.

Topics: Agranulocytosis; Cell Transformation, Neoplastic; Colony-Stimulating Factors; Cyclophosphamide; DNA; Humans; Leukocyte Count; Male; Melphalan; Middle Aged; Multiple Myeloma; Neutropenia; Neutrophils; Nitrosourea Compounds; Periodicity; Prednisone

Unscheduled DNA synthesis (UDS) induced by melphalan, nitrogen mustard and ultra-violet irradiation was studied in bone marrow cells from myeloma patients. In a previous study, normal bone marrow cells in various stages of maturation were found to display a gradual decrease in UDS parallel with the process of maturation. Myeloma cells showed a similar pattern. Poorly differentiated myeloma cells exhibited a similar level of UDS to myeloblasts and erythroblasts. Irrespective of which repair-inducing agent was used, the relationship between the levels of UDS in the various cell types was constant. This indicates that the differences in the level of UDS in the various cell types was not due to differences in the uptake of the repair-inducing agent.

Topics: Alkylating Agents; Bone Marrow; Cell Transformation, Neoplastic; DNA; Humans; Mechlorethamine; Melphalan; Multiple Myeloma; Time Factors; Ultraviolet Rays

Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

Topics: Cell Transformation, Neoplastic; Drug Therapy, Combination; Humans; Melphalan; Multiple Myeloma; Myeloma Proteins; Nitrosourea Compounds; Prednisone; Remission, Spontaneous; Time Factors

In order to get a better understanding of tumor biology, prognostic factors and approaches to treatment, total body tumor cell number, cell kinetics and drug sensitivity have been studied in a series of patients with multiple myeloma. We found that the presenting tumor mass stage was inversely proportional to survival, but did not predict drug sensitivity. Patients with both a high tumor cell mass and a large proliferative compartment of tumor cells had a particularly poor prognosis. Studies of myeloma stem cells in agar culture showed individual patterns of drug sensitivity with a correlation between in vitro sensitivity to melphalan, adriamycin, and BCNU, with in vivo sensitivity to these same classes of agents. Use of such measurements may permit selection of useful new drugs as well as an individualized basis for treatment of multiple myeloma.

Topics: Carmustine; Cell Transformation, Neoplastic; Doxorubicin; Drug Resistance; Humans; Melphalan; Multiple Myeloma; Neoplasm Staging; Prognosis

Various cancer chemotherapeutic agents including alkylating agents, antimetabolites, and antibiotics or natural products were studied for their ability to produce morphological transformation in the C3H/10T1/2 clone 8 mouse cell line and chromosomal damage in the A(T1)C1-3 hamster cell line following a 24-hr exposure of each agent at different concentrations. Those drugs that were known to be carcinogenic in vivo also produced morphological transformation and chromosomal damage, whereas those agents that have not been shown to be carcinogenic in vivo produced neither transformation nor chromosomal lesions. The concentrations used for these studies were in general similar to those actually reached in the plasma of patients treated with these same drugs for malignant, as well as certain nonmalignant, conditions.

Topics: Antineoplastic Agents; Bleomycin; Carcinogens; Cell Transformation, Neoplastic; Cells, Cultured; Chromosomes; Cytarabine; Dactinomycin; Drug Evaluation, Preclinical; Hycanthone; Melphalan; Mercaptopurine; Methotrexate; Mutagens; Tilorone; Vincristine

Topics: Cell Transformation, Neoplastic; Humans; Leukemia; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Time Factors

Five mammary tumours induced in rats by 7, 12-DMBA were each divided into four sections, and studied as cell suspensions in vitro for response to melphalan or progesterone measured as H3-thymidine incorporation. Heterogeneity towards melphalan and progesterone was found within all five tumours, but the mode of reaction of the two drugs differed. The biological relevance of these findings is discussed.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Cell Transformation, Neoplastic; Cells, Cultured; Female; Mammary Neoplasms, Experimental; Melphalan; Progesterone; Rats

Topics: Adenocarcinoma; Animals; Antilymphocyte Serum; Cell Survival; Cell Transformation, Neoplastic; Cyclophosphamide; Female; Immunosuppression Therapy; Mammary Neoplasms, Experimental; Melphalan; Mice; Mice, Inbred DBA; Time Factors

Topics: Animals; Cell Transformation, Neoplastic; Cytarabine; Depression, Chemical; DNA, Neoplasm; Drug Resistance; Female; In Vitro Techniques; Leukocyte Count; Melphalan; Methylcholanthrene; Mice; Neoplasm Transplantation; Sarcoma, Experimental; Stimulation, Chemical; Thymidine; Time Factors; Transplantation, Homologous; Tritium; Vinblastine

Topics: Adult; Aged; Bone Marrow; Bone Marrow Cells; Cell Division; Cell Nucleus; Cell Transformation, Neoplastic; DNA, Neoplasm; Female; Glucocorticoids; Humans; Kinetics; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasma Cells; Spectrophotometry; Thymidine; Tritium