Antimutagenic effect of rat small intestine in vitro on 1,1,2,3-tetrachloropropene and 1,1,2,3,3-pentachloropropene

Abstract

The direct mutagenic activity of 1,1,2,3-tetrachloropropene and 1,1,2,3,3-pentachloropropene in Salmonella typhimurium was measured before and after incubation in the presence of intact segments of rat small intestine in vitro. The number of revertants in tester strain TA100 was reduced by about 95% when these chloropropenes were exposed to rat small intestine for 10–30 min immediately prior to determination of mutagenicity. The existence of an intestine-mediated detoxication reaction was postulated, and was supported by observations that incubation with the chloropropenes for 30 min caused a 48–68% depletion of intestinal glutathione in vitro. Although addition of glutathione to the chloropropenes reduced mutagenicity, the amount of tissue glutathione consumed during incubation of mutagen with intestinal segments is probably insufficient to account for the detoxication. Additional metabolic reactions and/or non-specific protein binding may occur in the intact intestine which contribute to the antimutagenic effect. These initial results support the existence of an effective detoxication mechanism by the small intestine which is likely to reduce the absorption of direct-acting mutagens and other electrophiles.