Both exposure to genotoxicants, which initiate tumors, and exposure to bioretained chlorinated hydrocarbon tumor promoters, during the perinatal period may contribute to human cancer risk. A prominent member of the aryl amine food mutagen class, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is metabolically activated by cytochrome P4501A2. Efforts have begun to assess metabolism as a susceptibility factor in IQ adult and perinatal tumorigenesis. Methods have been developed to permit rapid, simple assay of CYP1A2 from rodent tissues by use of methoxyresorufin as a specific substrate and for consistent Western immunoblot quantification of 1A2 protein. It was found that IQ specifically induced only 1A2 and its activities, by a factor of 2, in a process not controlled by the Ah locus. In an ongoing study of promotion of perinatally-initiated tumors by chlorinated hydrocarbons, liver and lung tumors caused in mice by transplacental or neonatal exposure to the environmental nitrosamines N- nitrosodimethylamine (NDMA) or 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) were promoted by a single dose of Aroclor 1254 given later, with differences related to time of treatment, type of initiator, and sex, suggesting possible influences of both quantitative and qualitative factors (cf. project Z01CP05299). A new initiative has involved investigation of effects of preconception exposure of parents on tumors developed in their offspring. In a test of the hypothesis that exposure of fathers to metals may increase risk of cancer in their offspring, male mice were treated with metals typically present in welding fumes, 2 weeks before mating; increased incidence of lung tumors occurred after treatment of fathers with Fe, Ni, Mn, Co, and Cr, with an 8-fold effect (P = 0.02) after Cr (III). Derangement of epigenetic imprinting was proposed as a possible mechanism of this effect.
