A comparative investigation of DNA adducts, DNA strand breaks and gene mutations induced by benzo[a]pyrene and (+/-)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide in cultured human cells.
Genotoxic effects of benzo[a]pyrene (BP) and its reactive metabolites (+/-)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide ((+/-)-anti-BPDE) were comparatively investigated in vitro with the permanent human fibroblast cell line MRC5CV1. Induced DNA adducts were measured by 32P-postlabeling, DNA strand breakage was determined by the comet assay and the HPRT gene mutation test was used to detect cytotoxicity and mutagenicity. Treatment of MRC5CV1 cells with S9 mix-activated BP or with (+/-)-anti-BPDE resulted in a concentration-dependent increase in DNA adducts and strand breaks. Genotoxic effects of BP and (+/-)-anti-BPDE were detected by 32P-postlabeling and the comet assay with similar sensitivity. However, under the same experimental conditions, a clear induction of gene mutations was only found after (+/-)-anti-BPDE treatment. The relationship between the induction of primary DNA alterations like DNA strand breaks and DNA adducts and the induction of gene mutations is discussed.
Hanelt
S
S
Universität Ulm, Abteilung Medizinische Genetik, Germany.
Helbig
R
R
Hartmann
A
A
Lang
M
M
Seidel
A
A
Speit
G
G
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis* / Q000187:drug effects; D004249:DNA Damage; D004586:Electrophoresis / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D005821:Genetic Techniques; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000187:drug effects / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D010761:Phosphorus Radioisotopes
D018736:DNA Adducts; D009153:Mutagens; D010761:Phosphorus Radioisotopes; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase