peplomycin and Body-Weight

We studied the acute toxicity and pathological effects of peplomycin adsorbed on fine activated carbon particles (PEP-CH) injected subcutaneously in mice. The 50% lethal dose value was 41.2 mg/kg in terms of peplomycin, which was 1.52 times that of the peplomycin aqueous solution (PEP-AQ) of 27.1 mg/kg. Deaths occurred from 5 to 31 days after administration of PEP-CH and from 5 to 22 days after administration of PEP-AQ solution. These figures are remarkably different from another report in which the mice given PEP-AQ died within 10 days.

Topics: Adsorption; Animals; Body Weight; Carbon; Lethal Dose 50; Male; Mice; Mice, Inbred C3H; Organ Size; Peplomycin; Suspensions

Rats were treated for 1 week each with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.2% N-bis(2-hydroxypropyl)-nitrosamine (DHPN) and 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water, and then administered diet containing 5% sodium L-ascorbate (Na-AsA), 1% butylated hydroxytoluene (BHT) or 0.05% phenobarbital (PB), or weekly intraperitoneal injections of 2 mg of pepleomycin per kg body weight until week 36. Histopathological examination revealed that all exerted significant modulation effects on tumor development in the various target organs. Na-AsA was found to inhibit liver but promote renal pelvis and bladder carcinogenesis. BHT similarly decreased liver and enhanced bladder lesion development. PB, in contrast promoted hepatocarcinogenesis. However both PB and BHT were associated with increased incidences of adenomas and adenocarcinomas of the thyroid. Thus the wide-spectrum initiation model allowed confirmation of site-specific modification potential and in addition demonstrated potentiation of kidney and bladder carcinogenesis promotion by pepleomycin.

Topics: Animals; Ascorbic Acid; Bleomycin; Body Weight; Butylated Hydroxytoluene; Cocarcinogenesis; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms, Experimental; Peplomycin; Phenobarbital; Rats; Rats, Inbred F344; Thyroid Neoplasms; Urinary Bladder Neoplasms

In order to clarify the toxicity of the antineoplastic drugs, bleomycin (BLM), peplomycin (PEP) and cis-diamminedichloroplatinum (CDDP), which are commonly used to treat head and neck cancer by simultaneous administration, the semiacute toxicity of each of these drugs in rats was studied as an initial step. Body-weight change, general behavior, red blood cell count (RBC), white blood cell count (WBC), serum biochemistry (s-GOT, s-GPT, BUN, GLU, ALB, TP), A/G ratio, relative organ weight and histopathological features were determined. BLM and PEP given by ip administration once a week produced severe diarrhea, decreased diet consumption, emaciation, piloerection and loss of hair, enhancements of RBC and WBC, several changes in serum biochemistry, proliferation and mitosis of epithelial cells in the forestomach and occasional granular and vacuolar degeneration in the liver. CDDP administered in the same manner produced a significant decrease of WBC, several changes in serum biochemistry parameters especially BUN, an increased focal-segmental mesangial matrix in the glomeruli and vacuolar degeneration of epithelial cells of the convoluted tubule of the kidney.

Topics: Animals; Bleomycin; Blood Urea Nitrogen; Body Weight; Diarrhea; Erythrocyte Count; Liver; Male; Organ Size; Organoplatinum Compounds; Peplomycin; Rats; Rats, Inbred Strains; Stomach; Weight Loss

A single s.c. injection of 30 mg/kg of pepleomycin in mice produced an irreversible state of motor excitation and agitation from about 5 days after the injection, with the animals being very active and running around persistently (2-3 times/s). Abnormal movements persisted for the life of the animal without a further injection.

Topics: Animals; Bleomycin; Body Weight; Central Nervous System Agents; Female; Male; Mice; Mice, Inbred ICR; Motor Activity; Peplomycin; Seizures; Stereotyped Behavior

To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha-reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha-Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha-reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate

Topics: Animals; Antineoplastic Agents; Bleomycin; Body Weight; Cholestenone 5 alpha-Reductase; Cisplatin; Cyclophosphamide; Dactinomycin; Doxorubicin; Male; Mechlorethamine; Methotrexate; Organ Size; Oxidoreductases; Peplomycin; Prostate; Rats; Vinblastine; Vincristine

Bleomycins (BLM) are widely used as antineoplastic agents either alone or in combination regimens. Results of earlier studies in experimental animals were said to be inadequate to evaluate the carcinogenicity of BLM, which is a known mutagen. In a dose-response study, BLM and peplomycin (PEP) were investigated in Sprague-Dawley rats of both sexes. For the first 10 weeks weekly doses of 0.35, 0.70, 1.40, and 2.80 mg/kg BLM and of 0.32, 0.63, 1.25, 2.50, and 5.0 mg/kg PEP were applied subcutaneously (BLM: 30 male and 30 female rats/group; PEP: 25 male and 25 female rats/group). In the case of BLM, thereafter the doses were given once every fortnight either for 1 year (BLM: 1.40 and 2.80) or for life (lower doses). In the case of PEP, application of the high doses was stopped after the 13th time (5.0: 10 X 1/week and 3 X 1 every 2 weeks) and the 19th application (2.5 mg: 10 X 1/week and 9 X 1/every 2 weeks). After the 10th dosing, the remaining groups were treated once every fortnight for life. 60 male and 60 female rats served as solvent-treated (physiological saline) controls. The animals were observed for life. Repeated doses of BLM and PEP reduced body weight and life expectancy of the animals in a dose-related pattern. Tubular cell damages and cell proliferations were seen as a symptom of major toxicity in the kidneys. In this model BLM and PEP are carcinogenic: treatments resulted in significant dose-related incidences of animals with tumors at the site of application (fibrosarcomas) and with renal tumors (adenomas, adenocarcinomas, sarcomas).

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Body Weight; Carcinogens; Dose-Response Relationship, Drug; Female; Injections, Subcutaneous; Kidney Neoplasms; Male; Peplomycin; Rats; Risk; Sex Factors; Skin Neoplasms; Time Factors

The effect of peplomycin by three different treatment schedules was studied in mice bearing Ehrlich Effeit of carcinoma. continuous i.p. infusion of peplomycin via an osmotic minipump was compared to those by intermittent injection and daily injection. Equivalent total doses of the drug were administered in all three schedules. Continuous infusion for 7 days produced marked inhibition of tumor growth, which was significantly better than intermittent injection or daily injection of the same total dose. The effect of bleomycin by continuous infusion was significantly better than that by intermittent injection, but was as equally effective was daily injection. The results indicate that the continuous infusion of peplomycin is a useful treatment method.

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Body Weight; Carcinoma, Ehrlich Tumor; Mice; Mice, Inbred ICR; Peplomycin