The repair of large DNA adducts in mammalian cells.
This paper describes experiments involving the measurement of DNA damage and repair after treatment with 4-nitroquinoline 1-oxide (4NQO) or aflatoxin B1 (AFB1) epoxide in a number of mammalian cell cultures primarily associated with defects in the excision repair of UV-induced DNA damage. The results with transformed derivatives of XP cells belonging to different complementation groups showed that the extent of repair of 4NQO adducts at the N2 or C8 of guanosine did not correlate to the extent of repair reported by others after UV-irradiation. An examination of 4NQO repair in rodent UV-sensitive cell lines from different ERCC groups indicated that again there was little correlation between the extent of 4NQO and UV repair. However, regardless of complementation group those mutants that were defective in the repair of pyrimidine dimers and 6,4-photoproducts did exhibit a reduced ability to repair the 4NQO N2 guanosine adduct, whereas those mutants defective in pyrimidine dimer repair alone were able to repair this lesion as normal. In all of these cell lines there was a normal capacity to repair the 4NQO C8 guanosine adduct. Less extensive experiments involving AFB1 epoxide showed an XPC-transformed cell line was able to repair 40% of lesions after 6 h, whereas only 20% of repair is seen after UV. The rodent mutant V-C4 which belongs to the same ionising radiation group as irs2, was partially defective in repairing AFB1-induced damage. These experiments highlight the fact that although there are many commonalities between the repair of UV damages and lesions classed as large DNA adducts differences clearly exist, the most striking example here being the repair of the C8 guanosine 4NQO adduct which rarely correlates with a defect in UV repair.
Waters
R
R
Molecular Biology Research Group, School of Biological Sciences, University College of Swansea, Singleton Park, Great Britain.
Jones
C J
CJ
Martin
E A
EA
Yang
A L
AL
Jones
N J
NJ
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D002461:Cell Line, Transformed; D002470:Cell Survival; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D006801:Humans; D009154:Mutation; D014466:Ultraviolet Rays
D015112:4-Nitroquinoline-1-oxide; D004247:DNA; D016604:Aflatoxin B1