Inhibitory effect of hemin on mutagenicity of the electrophilic sulfuric acid ester of 6-hydroxymethylbenzo[a]pyrene.
In the present study, we examined the effects of hemin on the mutagenicity of 6-sulfooxymethylbenzo[a]pyrene (SMBP) in Salmonella typhimurium TA98 and Chinese hamster lung fibroblast (V79) cells. The compound was tested for the possible chemoprotective activity against mutagenesis induced by SMBP and its precursor, 6-hydroxymethylbenzo[a]pyrene (HMBP), activated by hepatic cytosol and PAPS in S. typhimurium TA98. Hemin not only inhibited the mutagenic activity of SMBP in V79 cells but repressed the cytotoxicity induced by this reactive ester as demonstrated by increased cell growth. The intracellular accumulation of radioactivity in V79 cells exposed to [3H]SMBP was reduced by approximately 50% when hemin (10 microM) was added to the medium. Likewise, the formation of SMBP-DNA adducts in these cells was significantly attenuated by treatment with hemin. The covalent complex formation of hemin with SMBP was confirmed by solvent extraction and reverse-phase HPLC.
Hong
S T
ST
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, Japan.
Cho
Y S
YS
Surh
Y J
YJ
Chung
A S
AS
D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D003412:Cricetulus; D018736:DNA Adducts / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001580:Benzopyrenes; D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; C066039:6-sulfooxymethylbenzo(a)pyrene; D006427:Hemin