The effects of carcinogens encountered during the perinatal period are modulated by (1) the capacity of perinatal tissues to activate the chemicals and (2) postnatal tumor promotive influences, among other factors. With regard to activation, attention is currently being focused on formation of DNA adducts by benzo[a]pyrene (BP) in the placenta and fetal tissues of patas monkeys, assayed by 32P-postlabeling (with Dr. L.J. Lu, see Project ZOICPO5092); and on effects of the arylamine food mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). IQ is activated metabolically by cytochrome P45OIA2, with several other isozymes contributing to detoxification. A study of transplacental carcinogenesis by IQ in mice and hamsters is ongoing. Preliminary to investigation of ontogeny of IQ metabolism as related to tumorigenesis, the effects of IQ as an enzyme inducer is being studied in mice. Significant increases in a cytochrome P45OIAI enzyme activity and decreases in total cytochrome P450 in C57BL/6 mice were noted. Study of tumor promotive influences has concentrated on the actions of retained congeners of polyclorinated biphenyls (PCBs), after a single dose of the mixture Aroclor 1254, and of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A preliminary study of the effects of restriction in dietary fat after PCB treatment showed that weight loss increased toxicity and increased level of induction of a specific cytochrome P450 isoform associated with tumor promotion, presumably due to release of stored PCB congeners from fat depots (see also project ZOICPO5299). A single dose of TCDD had persistent, organ-specific inducing effects, with lung being more sensitive than liver to continued induction after low doses of TCDD.
