methylnitronitrosoguanidine and Xeroderma-Pigmentosum

The radioprotective effect of the Bowman-Birk protease inhibitor (BBI) was previously shown to result from a TP53 dependent mechanism. Whether this effect involves specific DNA repair mechanisms is now tested.. Normal human fibroblasts were pre-treated with BBI before exposure to X-rays, UVB or to chemical agents (bleomycin, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cisplatin). These agents were chosen because of their ability to induce different spectra of DNA damage. The radiometric agent bleomycin primarily induces double-strand breaks (dsb), which are repaired by recombination; MNNG results in alkylated bases which are repaired by base excision repair (BER); cisplatin results in DNA-crosslinks which are repaired mainly by nucleotide excision repair (NER); and finally UVB generates thymine dimers and thymine-cytosine-6-4 products which are also repaired by NER. Cell survival was analysed by colony formation assay and DNA dsb by constant field gel electrophoresis. The combined effect of BBI and X-rays was also tested for XP-fibroblasts, which are defective in NER.. For normal human fibroblasts the radioprotective effect of BBI was clearly found by using a delayed plating procedure. The radioprotective effect was found to be unrelated to an altered induction or repair of radiation-induced DNA dsb. Pretreatment with BBI did not affect cell killing after exposure to bleomycin or MNNG, but resulted in a significant protection of cells exposed to cisplatin or UVB. These results indicate that pre-treatment with BBI did not alter recombination repair or BER, but was able to modify NER. The latter finding was supported by the observation made for XP-cells, where pretreatment with BBI failed to result in radioprotection after exposure to ionizing radiation.. On the basis of these data it is proposed that the radioprotective effect of BBI is the result of an improved nucleotide excision repair mechanism.

Topics: Bleomycin; Cell Survival; Cells, Cultured; Cisplatin; DNA Repair; Humans; Methylnitronitrosoguanidine; Protease Inhibitors; Radiation-Protective Agents; Ultraviolet Rays; X-Rays; Xeroderma Pigmentosum

Xeroderma pigmentosum complementation group E binding factor (XPE-BF) is a damaged DNA binding protein that is deficient in a subset of patients from complementation group E of xeroderma pigmentosum. The protein recognizes various forms of DNA damage including some cyclobutane pyrimidine dimers, 6-4 photoproducts, cis-diamminedichloroplatinum(II) adducts, and single-stranded DNA. We now show that it also recognizes damage induced by nitrogen mustard; N-methyl-N'-nitro-N-nitrosoguanidine, and depurination, but has no detectable affinity for DNA adducts generated by trans-diamminedichloroplatinum(II), 4-nitroquinoline-N-oxide, 8-methoxypsoralen, or enzymatically methylated cytosine and adenine. The failure to recognize 4-nitroquinoline-N-oxide and 8-methoxypsoralen adducts is consistent with previous reports that XPE cells carry out wild-type levels of repair synthesis after DNA damage by those drugs. These results demonstrate that XPE-BF is a versatile damage recognition protein, but suggest that other proteins must contribute to the recognition of DNA lesions for the human excision repair pathway.

Topics: 4-Nitroquinoline-1-oxide; Cisplatin; DNA; DNA Damage; DNA Repair; DNA-Binding Proteins; Genetic Complementation Test; HeLa Cells; Humans; Mechlorethamine; Methoxsalen; Methylnitronitrosoguanidine; Mutagens; Ultraviolet Rays; Xeroderma Pigmentosum

Human xeroderma pigmentosum (XP) fibroblasts were transformed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The transformed cells, called ASKMN, were immortalized, grew in agar and were tumorigenic in nude mice. A trp-met oncogene was identified in ASKMN cells, after transfection of high molecular weight DNA on 3T3 mouse cells. The ASKMN cells and the 3T3 transformants expressed the 5-kb mRNA transcribed by the tpr-met oncogene and its p65tpr-met phosphorylated protein. Using the polymerase chain reaction (PCR) technique followed by hybridization with synthetic probes or direct sequencing, we showed that the sequence encompassing the 'rearranged breakpoint' was the same as that previously described in the tpr-met oncogene present in the MNNG-HOS cells. However, G to A transitions found in the tpr or met sequences of the ASKMN oncogene, probably the result of the specific mutagenic activity of MNNG, were absent in the MNNG-HOS gene. Apparently normal chromosomes 1 and 7 were identified in the ASKMN cell metaphases using several cytogenetic techniques.

Topics: Animals; Base Sequence; Cell Line; Cell Transformation, Neoplastic; Child; Chromosome Aberrations; Gene Expression Regulation; Humans; Karyotyping; Methylnitronitrosoguanidine; Mice; Molecular Sequence Data; Proto-Oncogene Mas; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-met; Proto-Oncogenes; RNA, Messenger; Xeroderma Pigmentosum

Levels of 5'-adenyl dinucleotides, measured as diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A), were found to accumulate in cultured human fibroblasts following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the radiomimetic drug bleomycin, and nitroquinoline-1-oxide (NQO) or UV-irradiation in the presence of cytosine arabinofuranoside (araC). In contrast, cells derived from patients with xeroderma pigmentosum complementation group A (XP-A) did not demonstrate an increase in DNA-strand breaks following UV irradiation or NQO in the presence of araC nor an increase in Ap4A levels. Ap4A accumulation did occur in XP-A cells following treatment with MNNG. Cells derived from patients characterized as XP variants, which are incision repair-proficient, accumulated 5'-dinucleotides following bleomycin, MNNG and UV or NQO in the presence of araC. Taken together, these data suggest that Ap4A accumulates as a response to DNA-strand breaks.

Topics: 4-Nitroquinoline-1-oxide; Adenine Nucleotides; Bleomycin; Cytarabine; Dinucleoside Phosphates; DNA Damage; Fibroblasts; Humans; Methylnitronitrosoguanidine; Ultraviolet Rays; Xeroderma Pigmentosum

A group A xeroderma pigmentosum revertant with normal sensitivity was created by chemical mutagenesis. It repaired (6-4) photoproducts normally but not pyrimidine dimers and had near normal levels of repair replication, sister chromatid exchange, and mutagenesis from UV light. The rate of UV-induced mutation in a shuttle vector, however, was as high as the rate in the parental xeroderma pigmentosum cell line.

Topics: 4-Nitroquinoline-1-oxide; Cell Line, Transformed; DNA Repair; Humans; Methylnitronitrosoguanidine; Mutation; Pyrimidine Dimers; Sister Chromatid Exchange; Ultraviolet Rays; Xeroderma Pigmentosum

When cells of a human clonal cell line, RSa, with high sensitivity to UV lethality, were treated with the mutagen, ethyl methanesulfonate, a variant cell strain, UVr-1, was established as a mutant resistant to 254-nm far-ultraviolet radiation (UV). Cell proliferation studies showed that UVr-1 cells survived and actively proliferated at doses of UV-irradiation that greatly suppressed the proliferation of RSa cells. Colony-formation assays also confirmed the increased resistance of UVr-1 cells to UV. The recovery from a UV-induced inhibition in DNA synthesis, as [methyl-3H]thymidine uptake into cellular DNA, was more pronounced in UVr-1 cells than in RSa cells. Nevertheless, there was no significant difference in the activity of UV-induced DNA repair synthesis in either cell line, as estimated by the extent of unscheduled DNA synthesis and DNA repair replication. UVr-1 cells were also more refractory to 4-nitroquinoline 1-oxide (4NQO), but the activity of DNA repair synthesis induced by 4NQO in UVr-1 cells was much the same as in the RSa cells. Both N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) sensitivity and MNNG-induced DNA repair synthesis activity in UVr-1 cells were similar to that of RSa cells. These characteristics of UVr-1 cells are discussed in the light of a previously reported UV-resistant variant, UVr-10, which had an increased DNA repair synthesis activity.

Topics: 4-Nitroquinoline-1-oxide; Cell Cycle; Cell Line; Cell Survival; Clone Cells; DNA Repair; DNA Replication; Dose-Response Relationship, Radiation; Humans; Kinetics; Methylnitronitrosoguanidine; Ultraviolet Rays; Xeroderma Pigmentosum

The influence of caffeine on cytotoxicity and postreplication repair of DNA was examined following exposure of several cell types to physical and chemical agents known to damage DNA. The cell types used in this study were normal human fibroblasts (HS-WP), human xeroderma pigmentosum fibroblasts (SGL), Chinese hamster V79 cells, mouse BALB/c-3T3 cells, and secondary Syrian hamster embryo cells. The DNA damaging agents were ultraviolet light (UV), N-2-acetoxy-fluorenylacetamide (AFAA), nitroquinoline-N-oxide (NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Induction of cytotoxicity in Chinese hamster V79 cells due to ultraviolet light or AFAA exposure was enhanced by caffeine at a concentration of 1.0 mM in the culture medium, but not at 0.2 or 0.05 mM. Caffeine also inhibited postreplication repair in these cells at the same concentrations. In contrast, postreplication repair was not affected by caffeine at concentrations up to 1.0 mM in normal human fibroblasts (HS-WP), human xeroderma pigmentosum fibroblasts (SGL), secondary Syrian hamster embryo cells, and mouse BALB/c-3T3 cells following treatment with ultraviolet light, AFAA, NQO, or MNNG. Cytotoxicity in BALB/c-3T3 cells following exposure to ultraviolet light or AFAA was enhanced in the presence of caffeine at 1.0 or 0.2 mM, although these concentrations of caffeine had no effect on postreplication repair in these cells. The inhibitory effect of caffeine on postreplication repair was found only in Chinese hamster V79 cells among the five cell types used in this study. Both normal and xeroderma pigmentosum human cells repaired mutagen-induced DNA damage equally well in the absence or presence of caffeine at concentrations of 1.0 mM or less.

Topics: 2-Acetylaminofluorene; 4-Nitroquinoline-1-oxide; Animals; Caffeine; Cell Line; Cell Survival; Cricetinae; Cricetulus; DNA Repair; Drug Synergism; Embryo, Mammalian; Fibroblasts; Humans; Mesocricetus; Methylnitronitrosoguanidine; Mice; Mice, Inbred BALB C; Mutagens; Ultraviolet Rays; Xeroderma Pigmentosum

The effects of hydroxyurea on plaque formation by UV-irradiated and MNNG-treated adenovirus 5 were investigated. Hydroxyurea blocked the recovery of UV-irradiated viruses in all cases studied, but the effect was less when fibroblasts from a patient with xeroderma pigmentosum were used. This fact supports the notion that hydroxyurea blocks excision repair of UV-produced damage. The recovery of MNNG-treated viruses was not blocked by hydroxyurea when viruses were used to infect normal human fibroblasts, but was blocked if the cell strain used as viral host were deficient in repair of O6-methylguanine. To account for these data, we propose that hydroxyurea blocks repair in which DNA polymerases play a role, but does not block repair in which DNA polymerases are not required.

Topics: Adenoviruses, Human; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Fibroblasts; Humans; Hydroxyurea; Methylnitronitrosoguanidine; Ultraviolet Rays; Xeroderma Pigmentosum

The UV-endonuclease approach to detect DNA damage has been combined with the alkaline elution technique with a resultant marked increase in sensitivity compared to the conventional method using alkaline sedimentation. DNA from UV-irradiated cells was digested on an inert filter with an extract from Micrococcus luteus and then analyzed by alkaline elution. Endonuclease-sensitive sites (endo-sites) were measured after doses of 0.08-0.7 Jm-2 of UV-radiation. An estimate of endo-site production with UV radiation, 0.27 endo-sites/10(8) daltons of DNA/0.1 Jm-2, was similar to that usually seen at higher doses by others. With repair incubation, approx. 50% of the endo-sites were removed in 4 h by normal human fibroblasts after 0.2 or 0.4 Jm-2; no appreciable repair was seen in xeroderma pigmentosum fibroblasts from complementation group A after 24 h of repair incubation. No photoreaction of UV damage due to 0.4 Jm-2 was detected in normal human fibroblasts. The endonuclease preparation also recognized DNA damage produced by ionizing radiation or an alkylating agent. Approx. 0.4 endo-sites/10(8) daltons of DNA were detected after a dose of 1 krad and 1 endo-site/10(8) daltons was observed after exposure of human cells to 2.5 microM MNNG for 1.3 h. The lesions detected after MNNG treatment by the endonuclease preparation decreased with post-treatment incubation--T1/2 8 h. The kinetics of removal of the endo-sites induced by MNNG were similar in normal cells and human cells of the mer- phenotype which has been shown to be more sensitive by cell killing to alkylating-agent damage. This should prove to be a useful approach to study DNA damage and repair since the entire assay can be done in several hours and a very low level of damage (1 endo-site/2 x 10(9) daltons of DNA) can be detected.

Topics: Cell Line; DNA; DNA Replication; Humans; Hydrogen-Ion Concentration; Kinetics; Methylnitronitrosoguanidine; Micrococcal Nuclease; Micrococcus; Molecular Weight; Xeroderma Pigmentosum

Novobiocin and nalidixic acid, inhibitors of the bacterial enzyme DNA gyrase, inhibit DNA, RNA and protein synthesis in several human and rodent cell lines. The sensitivity of DNA synthesis (both replicative and repair) to inhibition by novobiocin and nalidixic acid is greater than that of protein synthesis. Novobiocin inhibits RNA synthesis about half as effectively as it does DNA synthesis, whereas nalidixic acid inhibits both equally well. Replicative DNA synthesis, as measured by incorporation of [3H]thymidine, is blocked by novobiocin in a number of cell strains; the inhibition is reversible with respect to both DNA synthesis and cell killing, and continues for as long as 20--30 h if the cells are kept in novobiocin-containing growth medium. Both novobiocin and nalidixic acid inhibit repair DNA synthesis (measured by BND-cellulose chromatography) induced by ultraviolet light or N-methyl-N'-nitro-N-nitrosoguanidine (but not that induced by methyl methanesulfonate) at lower concentration (as low as 5 micrograms/ml) than those required to inhibit replicative DNA synthesis (50 micrograms/ml or greater). Neither novobiocin nor nalidixic acid alone induces DNA repair synthesis. Incubation of ultraviolet-irradiated cells with 10--100 micrograms/ml novobiocin results in little, if any, further reduction of colony-forming ability (beyond that caused by the ultraviolet irradiation). Novobiocin at sufficiently low concentrations (200 micrograms/ml) apparently generates a quiescent state (in terms of cellular DNA metabolism) from which recovery is possible. Under more drastic conditions of time in contact with cells and concentration, however, novobiocin itself induces mammalian cell killing.

Topics: Cell Line; Cell Survival; DNA; DNA Repair; DNA Replication; DNA Topoisomerases, Type I; DNA, Superhelical; Humans; Kinetics; Methylnitronitrosoguanidine; Nalidixic Acid; Novobiocin; Xeroderma Pigmentosum

Unscheduled DNA synthesis has been measured in human fibroblasts under conditions of reduced rates of conversion of NAD to poly)ADP-ribose). Cells heterozygous for the xeroderma pigmentosum genotype showed normal rates of UV induced unscheduled DNA synthesis under conditions in which the rate of poly(ADP-ribose) synthesis was one-half the rate of normal cells. The addition of theophylline, a potent inhibitor of poly(ADP-ribose) polymerase, to the culture medium of normal cells blocked over 90% of the conversion of NAD to poly(ADP-ribose) following treatment with UV or N-methyl-N'-nitro-N-nitro-soguanidine but did not affect the rate of unscheduled DNA synthesis.

Topics: Cell Line; DNA; DNA Repair; DNA Replication; Fibroblasts; Genotype; Heterozygote; Humans; Methylnitronitrosoguanidine; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose; Ultraviolet Rays; Xeroderma Pigmentosum

Treatment of normal human cells with DNA-damaging agents such as UV light or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stimulates the conversion of NAD to the chromosomal polymer poly(ADP-ribose) which in turn results in a rapid depletion of the cellular NAD pool. We have studied the effect of UV light or MNNG on the NAD pools of seven cell lines of human fibroblasts either homozygous or heterozygous for the xeroderma pigmentosum genotype. Xeroderma pigmentosum cells of genetic complementation groups A, C, and D are deficient in the excision repair of DNA damage caused by UV light. Following UV treatment, the NAD content of these cells was unchanged (complementation groups A and D) or only slightly reduced (complementation group C). Xeroderma pigmentosum cells with the variant genotype have normal excision repair and UV treatment caused a large reduction in the size of the NAD pool. Cell lines derived from asymptomatic, parental heterozygotes of xeroderma pigmentosum complementation groups A and D showed an amount of lowering of NAD following UV treatment that was approximately one-half that of the control cell line. All of the cell lines are able to excise DNA damage caused by MNNG and all of the cell lines had a greatly reduced content of NAD following MNNG treatment. The results demonstrate a close relationship between the conversion of NAD to poly(ADP-ribose) and DNA excision repair in human cells.

Topics: Cell Line; DNA; DNA Repair; Fibroblasts; Heterozygote; Homozygote; Humans; Kinetics; Methylnitronitrosoguanidine; NAD; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose; Ultraviolet Rays; Xeroderma Pigmentosum

The ability to excise (repair) UV-induced pyrimidine dimers in Escherichia coli is not related to its ability to remove N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced O6-methylguanine (O6-MeG) from DNA. It was therefore surprising that certain xeroderma pigmentosum cell lines, deficient in dimer excision, were also unable to remove O6-MeG. We find that removal of O6-MeG occurs rapidly with a half life of less than 1 h. Two cell types can be distinguished: mex+, which remove O6-MeG residues produced by incubation with 0.5 microgram ml-1 MNNG, and mex- cells, which are unable to remove the adduct. Xeroderma pigmentosum-derived lymphoblastoid lines of complementation groups A, C or D may be either mex+ or mex-. The biochemical mechanism for the removal of O6-MeG in human cells is distinct from the excision of adducts produced by compounds such as N-acetoxy-N-2-acetylaminofluorene (AAAF) or by UV irradiation but it is not clear whether the distinction between mex+ and mex- lines is genetic or epigenetic.

Topics: Alleles; Burkitt Lymphoma; Cells, Cultured; Deoxyadenine Nucleotides; Deoxyguanine Nucleotides; DNA Repair; Humans; Methylation; Methylnitronitrosoguanidine; Polymorphism, Genetic; Xeroderma Pigmentosum

Topics: Ataxia Telangiectasia; Cells, Cultured; DNA Repair; Dose-Response Relationship, Drug; Guanine; Humans; Kinetics; Methylnitronitrosoguanidine; Mutation; Xeroderma Pigmentosum

We established lymphoblastoid cell lines from 2 children with Chediak--Higashi syndrome (CHS), 2 xeroderma pigmentosum (XP) patients and control donors after transformation of peripheral lymphocytes by Epstein--Barr virus (EBV). We used these lymphoblastoid cell lines to investigate repair activity after ultraviolet irradiation. Cell survival of both CHS lymphoblastoid cell lines after irradiation by UV and treatment by 4-nitroquinoline 1-oxide (4NQO) fell between those of the XP and control cell lines. Unscheduled DNA synthesis of CHS cells after UV irradiation occurred at rates similar to those of control cells.

Topics: 4-Nitroquinoline-1-oxide; Cell Line; Cell Transformation, Viral; Chediak-Higashi Syndrome; DNA; DNA Repair; Herpesvirus 4, Human; Heterozygote; Humans; Lymphocytes; Methylnitronitrosoguanidine; Radiation Tolerance; Xeroderma Pigmentosum

Topics: Cell Line; Humans; Kinetics; Lymphocytes; Methylnitronitrosoguanidine; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose; Ultraviolet Rays; Xeroderma Pigmentosum

Mutants resistant to diphtheria toxin (Dipr) have been selected from a variety of human fibroblast cell strains derived from both normal subjects and individuals with known genetic predisposition to cancer such as xeroderma pigmentosum, Fanconi anemia and Bloom's syndrome. Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) led to a marked increase in the frequency of Dipr mutants in various cell strains. The increase in the frequency of Dipr mutants occurred in a linear dose-dependent manner in response to MNNG and ethyl methanesulfonate, in one of the cell strains examined. The rate of mutation to diphtheria toxin as determined by fluctuation analysis was very similar in various cell strains (1-3 x 10(-7) mutations/cell/generation), except for the strain GM1492 (8.8 x 10(-7) mutations/cell/generation) which is derived from a Bloom syndrome patient.

Topics: Anemia, Aplastic; Cell Line; Diphtheria Toxin; Dose-Response Relationship, Drug; Drug Resistance; Dwarfism; Ethyl Methanesulfonate; Fanconi Anemia; Humans; Methylnitronitrosoguanidine; Mutation; Photosensitivity Disorders; Syndrome; Xeroderma Pigmentosum

Lymphoblastoid cell derived from a complementation group C xeroderma patient were unable to remove 06-methyl guanine residues formed in DNA by treatment of cells with low concentration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The xeroderma cells were competent in their ability to excise 3-methyl adenine adducts. MNNG treatment induced excision repair in the xeroderma line and in addition the treatment resulted in the presence of numerous single-strand breaks in the DNA. The single gene, UV-excision-defective mutants of Escherichia coli, uvrA and uvrB, are able to excise MNNG-induced 06-methyl guanine adducts indicating that excision of this compound is not due to operation of UV endonuclease system.

Topics: Cell Line; DNA; DNA Repair; Dose-Response Relationship, Drug; Humans; Lymphocytes; Methylnitronitrosoguanidine; Mutagens; Phenotype; Xeroderma Pigmentosum

The sensitivity of cultured fibroblasts obtained from four unrelated Xeroderma pigmentosum patients (XP-K, XP-C, XP-E and XP-H), which showed different DNA repair levels, was examined. The frequency of metaphase plates with chromosome aberrations and the frequency of breaks and exchanges per chromosome complement were estimated following exposure to the carcinogens 4-nitroquinoline-1-oxide (4NQO),N-acetoxy-2-acetyl-aminofluorene (N-acetoxy-2-AAF), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and to the mutagen daunomycin. The frequency of chromosome aberrations (breaks and exchanges) increased in the order (XP-K less than XP-C less than XP-E less than XP-H) with decreasing DNA repair capacity of the XP cells examined (XP-K greater than XP-C greater than XP-E greater than XP-H) following 4NQO and N-acetoxy-2-AAF. MNNG induced DNA repair synthesis and chromosome aberrations in the four XP cell types at levels comparable to those in fibroblasts of non-afflicted persons. Daunomycin triggered no DNA repair synthesis but induced similar frequencies of chromosome aberrations in the XP cells and controls. Heterozygous XP cells from parents of XP-K, XP-E and XP-C responded as control cells towards the three carcinogens and the mutagen used. Xeroderma pigmentosum can be considered to be an "induced" chromosome instability syndrome, in contrast to Bloom's syndrome or Fanconi's anaemia, which are "spontaneous" chromosome breakage syndromes according to German's definition.

Topics: 4-Nitroquinoline-1-oxide; Acetoxyacetylaminofluorene; Carcinogens; Cells, Cultured; Chromosome Aberrations; Chromosomes; Daunorubicin; DNA Repair; Fibroblasts; Humans; Methylnitronitrosoguanidine; Mutagens; Xeroderma Pigmentosum

Topics: 9,10-Dimethyl-1,2-benzanthracene; Benz(a)Anthracenes; Benzopyrenes; Cell Survival; Cells, Cultured; DNA; DNA Repair; Epoxy Compounds; Fibroblasts; Humans; Methylnitronitrosoguanidine; Ultraviolet Rays; Xeroderma Pigmentosum

Topics: Carcinogens; Chromatids; Chromosome Aberrations; Crossing Over, Genetic; DNA Repair; Humans; Methylnitronitrosoguanidine; Mutagens; Stimulation, Chemical; Xeroderma Pigmentosum

Topics: Cell Line; Cell Transformation, Neoplastic; Fibroblasts; Humans; Methylnitronitrosoguanidine; Xeroderma Pigmentosum

Topics: Acetoxyacetylaminofluorene; Carcinogens; DNA Repair; DNA Replication; Methylnitronitrosoguanidine; Xeroderma Pigmentosum