Sensitivity and single-strand DNA break repair in Chinese hamster mutants exposed to the carcinogen aflatoxin B1 epoxide and its dichloride model.
Aflatoxin B1 (AFB1) is a potent carcinogen and mutagen. It requires metabolic activation to be converted to the DNA-binding product aflatoxin B1 epoxide (AFB1-epoxide). A model of this epoxide is aflatoxin B1 dichloride (AFB1Cl2). Both react at the N7 position of guanine to form large adducts. The major adduct formed can either be rapidly removed to leave an apurinic site or can undergo ring opening of the imidazole ring to form a chemically stable adduct. A number of Chinese hamster DNA repair-deficient mutants have been screened for their sensitivity to AFB1-epoxide and AFB1Cl2. Some of the mutants screened belong to different UV complementation groups. Human genes involved in nucleotide excision-repair correct deficiencies found in these complementation groups. The mutants which were found to be most sensitive to AFB1 (V-C4 and V-H1) were further investigated. Alkaline elution was used to measure AFB1-induced DNA single-strand break repair in the mutants. V-H1 repaired completely in 24 h whereas V-C4 displayed only partial repair.
Martin
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Molecular Biology Research Group, School of Biological Sciences, University College of Swansea, Wales, Great Britain.
Waters
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D016604:Aflatoxin B1 / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D015197:Carcinogenicity Tests; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000187:drug effects*; D009152:Mutagenicity Tests; D009154:Mutation / Q000235:genetics
D004277:DNA, Single-Stranded; C074511:aflatoxin B1-8,9-dichloride; C006426:aflatoxin B1-2,3-oxide; D016604:Aflatoxin B1