Differential effects induced by N-hydroxy-2-acetylaminofluorene and N-hydroxy-2-aminofluorene in DNA excision-repair-deficient Chinese hamster cells.
The direct-acting cytotoxic properties of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-2-aminofluorene (N-OH-AF) have been determined in repair-proficient (AA8-4) and repair-deficient (UV-5) Chinese hamster ovary cells. Cytotoxicity comparisons indicate that UV-5 cells are considerably more sensitive to exposure to N-OH-AAF than is the parental AA8-4 cell line, i.e., concentrations needed to obtain a D37 for survival of AA8-4 is greater than 5-fold higher than for UV-5. Mutation analysis at the HGPRT locus also indicates the increased sensitivity of UV-5 cells to N-OH-AAF as witnessed by an enhanced induction of 6-thioguanine-resistant colonies at equitoxic doses. Conversely, N-OH-AAF, did not induce a 'UV-mimetic' response when comparing genotoxicity between these two cell lines. Our data coupled with previously published model-building and adduct removal studies (Broyde and Hingerty, 1983; Fuchs and Daune, 1974; Grunberger and Weinstein, 1976; Yamasaki et al., 1977) suggest that the minor DNA adduct species, N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene, may be responsible for the hypermutagenicity witnessed in DNA excision-repair-deficient cells treated with N-OH-AAF.
Okinaka
R T
RT
Life Sciences Division, Los Alamos National Laboratory, NM 87545.
Whaley
T W
TW
Strniste
G F
GF
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004260:DNA Repair; D005449:Fluorenes / Q000633:toxicity*; D006881:Hydroxyacetylaminofluorene / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects*; D014466:Ultraviolet Rays
D005449:Fluorenes; D006881:Hydroxyacetylaminofluorene; C001368:N-hydroxy-2-aminofluorene; D015073:2-Acetylaminofluorene