Enhancing effect of a plastic plasticizer, di-2-ethylhexyl phthalate on umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002).
Di-2-ethylhexyl phthalate (DEHP) is the most extensively used phthalate ester as a plasticizer for plastic products made of polyvinyl chloride (PVC), and previous mutagenic and genotoxic studies have shown positive and negative results of DEHP-induced genotoxicity. To elucidate this discrepancy, we reestimated the genotoxicity of DEHP in more detail using the umu C gene expression system in Salmonella typhimurium (TA 1535/pSK 1002) which reflects SOS response against genotoxin-induced DNA damage. Although DEHP itself did not have a significant effect on umu C gene expression in tester bacteria at 0.5 to 4 mM, higher concentrations of DEHP (2 and 4 mM) caused a weak induction of umu C gene expression in the presence of commercially available S-9 mixture. Rat liver S-9 fraction alone also showed a similar weak inducing activity in the absence of substrates for drug-metabolizing enzymes. When DEHP was preincubated with S-9 fraction of various rat organs and applied to the umu C gene expression assay, S-9 fraction of rat pancreas had the strongest inducing activity, and S-9 fractions of liver and intestine homogenates showed weak but significant activities. However, S-9 fractions of lung and kidney homogenates did not exhibit any significant activities. These S-9 fractions have proportional lipase activities comparable with umu C gene expression activities. Furthermore, when DEHP was treated with highly purified lipase from porcine pancreas, a significant umu C gene expression was observed and this expression was enhanced in the presence of 1 or 5 mM bile acids such as choric acid and deoxychoric acid. These results suggest that DEHP itself has no or very low genotoxicity, but enzymatic and non-enzymatic factors in specific tissues induce DEHP-dependent genotoxic activity.
Okai
Y
Y
Department of Human Life Science, Osaka Kun-Ei Women's College, Showjaku, Sets City, Osaka 566-8501, Japan.
Higashi-Okai
K
K
D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005798:Genes, Bacterial / Q000235:genetics*; D008049:Lipase / Q000502:physiology; D008297:Male; D010968:Plasticizers / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000235:genetics*; D013552:Swine
D001647:Bile Acids and Salts; D010968:Plasticizers; D004051:Diethylhexyl Phthalate; D008049:Lipase