Comparison of the sites of reaction of three polycyclic aromatic hydrocarbons in the supF gene.
The distribution of hydrocarbon-DNA adducts through the supF gene in plasmid pS189 was examined using the polymerase arrest assay. For three hydrocarbon dihydrodiol epoxides, derived from 5-methylchrysene, 7-methylbenz[a]anthracene, and benzo[a]pyrene, that exhibit a preference for reaction with guanine residues in DNA, polymerase arrest spectra were similar but not identical. For each agent, guanines in different sequence contexts exhibited varying reactivities and each specific guanine did not necessarily respond to each agent in the same fashion. Thus, sequence context together with the individual dihydrodiol epoxide's chemical and physical properties all play a role in determining sites and extents of reaction within a specific gene. The polymerase arrest data were not predictive of the known sites of mutation hotspots for these dihydrodiol epoxides in the supF gene indicating that further action upon the adducted DNA by repair systems is probably necessary to determine which specific chemical adducts will ultimately give rise to mutation.
Ross
H L
HL
Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702.
Lee
H
H
Harvey
R G
RG
Dipple
A
A
D001483:Base Sequence; D001551:Benz(a)Anthracenes / Q000378:metabolism* / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism*; D002911:Chrysenes / Q000378:metabolism* / Q000633:toxicity; D004247:DNA / Q000378:metabolism* / Q000633:toxicity; D018736:DNA Adducts; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity; D008969:Molecular Sequence Data; D009154:Mutation; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D002911:Chrysenes; D018736:DNA Adducts; D004852:Epoxy Compounds; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004247:DNA; C021219:7-methylbenzanthracene; C008422:5-methylchrysene