Relationships between the DNA adducts and the mutations and sister-chromatid exchanges produced in Chinese hamster ovary cells by N-hydroxy-2-aminofluorene, N-hydroxy-N'-acetylbenzidine and 1-nitrosopyrene.
Chinese hamster ovary cells were exposed to N-hydroxy-2-aminofluorene, N-hydroxy-N'-acetylbenzidine and 1-nitrosopyrene, and the resulting DNA adducts, sister-chromatid exchanges (SCEs) and mutations at the hypoxanthine-guanine phosphoribosyl transferase locus were quantified. Each agent produced a major DNA adduct substituted through the C8 of deoxyguanosine. When the data from all three agents were combined, both mutation and SCE induction correlated strongly with the concentration of DNA adducts. However, significant differences were found in the relationships between adduct formation and the biological responses produced by the individual agents. While N-hydroxy-N'-acetylbenzidine induced the most mutations per adduct, N-hydroxy-2-aminofluorene caused the greatest number of SCEs per adduct. The data support the involvement of C8-deoxyguanosine adducts in mutation and SCE induction, and indicate that the structure of the group adducted to DNA may be an important factor in determining the magnitude of these biological responses. These findings also suggest that SCE and mutation induction are independent expressions of DNA damage.
Heflich
R H
RH
National Center for Toxicological Research, Jefferson, AR 72079.
Morris
S M
SM
Beranek
D T
DT
McGarrity
L J
LJ
Chen
J J
JJ
Beland
F A
FA
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001560:Benzidines / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000494:pharmacology*; D009154:Mutation; D011721:Pyrenes / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000477:Alkylating Agents; D001560:Benzidines; D005449:Fluorenes; D011721:Pyrenes; C001368:N-hydroxy-2-aminofluorene; C045050:N-hydroxy-N'-acetylbenzidine; C044707:1-nitrosopyrene