Antimutagenic properties of liver homogenates, proteins and glutathione on diesel exhaust particulates.
Diesel exhaust particulates contain mutagens which are active in the Ames Salmonella typhimurium assay. The mutagens do not require liver enzymes for activation and, in fact, the addition of liver homogenates (S-9) to the Ames system decreases the mutagenicity of diesel exhaust samples. We have examined here the properties and components of S-9 that account for its antimutagenic effect. The antimutagenic effect of S-9 is not changed by heating S-9 in a boiling water bath for 5 min or by omission of the NADPH-generating system in the cofactor mixture. These experiments showed that the antimutagenic effect on S-9 is not enzymatic. The antimutagenicity of S-9 disappeared after the protein component of S-9 was removed by filtration. Exogenous albumin added to the Ames system mimicked the antimutagenic effect. Analysis of the albumin content of liver cytosol showed that 90% of the antimutagenic effect could be accounted for by the amount of albumin present. Glutathione added to diesel exhausts reduced mutagenicity, but the qualities of glutathione present in S-9 are too small to account for the antimutagenic effect of S-9. We conclude that the antimutagenic effect of S-9 is non-enzymatic and is most likely the result of non-specific protein binding of mutagens to liver albumin. The antimutagenic effect of glutathione on diesel exhausts suggests that the mutagens present are electrophiles.
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D005978:Glutathione / Q000494:pharmacology*; D008110:Liver Extracts / Q000494:pharmacology*; D008297:Male; D009153:Mutagens / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001335:Vehicle Emissions / Q000633:toxicity*
D000418:Albumins; D008110:Liver Extracts; D009153:Mutagens; D011506:Proteins; D001335:Vehicle Emissions; D005978:Glutathione