Abstract
A number of organochlorine insecticides have been examined for both their in vitro and in vivo effects on the biphenyl system for detecting potential carcinogens. This test is based on previous findings that biphenyl 2-hydroxylase can be selectively enhanced by carcinogens. DDT, DDE, DDD and aldrin caused a statistically significant in vitro stimulation of biphenyl 2-hydroxylation after an initial preincubation period with liver microsomes. Dieldrin, however, elicited such a change without any preincubation. These increases were difficult to interpret since it was shown that at least part of the apparent stimulation produced by known carcinogens such as safrole, 3-methylcholanthrene and 3,4-benzpyrene, was due to the generation of fluorescent metabolites that interferred with the determination of 2-hydroxybiphenyl formation in the assay used. Single intraperitoneal administration of test chemicals to rats showed that the carcinogen, 3-methylcholanthrene, caused a selective enhancement of biphenyl 2-hydroxylase activity whereas phenobarbitone affected both the 2- and 4-hydroxylases to a similar extent. However, induction patterns observed for compounds such as alpha-benzene hexachloride, which is carcinogenic, or delta-benzene hexachloride, which is noncarcinogenic to rats, showed no differences. A long-term feeding study was carried out in rats with dietary DDT at 250 ppm and 500 ppm. Histological, histochemical and ultrastructural alterations in the liver were compared with sequential measurements of hepatic drug-metabolizing enzyme activity. Induction of these enzymes was observed within 10 days of feeding, and this was sustained throughout the experimental period. There was no evidence of liver injury in animals of either dose group up to the termination of treatment at 8 months.