Themes pursued included (1) transplacental risks of human exposure chemicals, (2) genetic determinants of perinatal cancer risk, (3) postnatal promotion of perinatally initiated tumors; and (4) promotion of mammary tumors by bioretained chlorinated aromatic hydrocarbons. cis- Dichlorodiammineplatinum, an anticancer agent sometimes used in pregnant women for the treatment of malignant ovarian and uterine tumors, was tested for transplacental tumor-initiating effects in SENCAR mice. Exposure to 7.5 mg/kg on gestation day 17 resulted in a significant increase in thymic lymphomas (16% vs 0% in controls), lung tumors (9% vs 1%), and promotable skin tumors (49% vs 10%). These results provide evidence that this drug can initiate neoplastic lesions in multiple tissues transplacentally. With regard to genetic determinants, DNA adducts of the metabolism-dependent carcinogen, 3-methylcholanthrene (MC) were assayed by 32P-postlabeling in mouse fetal tissues. Both parental and fetal genotypes at the Ah locus, which controls induction of cytochrome P450 1A1, influenced level of adduction, with greatest adducts in inducible fetuses carried in noninducible mothers, and least where both were noninducible. Postnatal promotion of tumors was studied after initiation of liver and lung tumors with N-nitrosodimethylamine (NDMA) on day 4 of life, followed by treatment on day 8 with the polychlorinated biphenyls (PCBs) mixture, Aroclor 1254. Incidences of NDMA-initiated lung tumors were enhanced by PCBs 2.5-fold at 28 weeks, and multiplicities fourfold at 28 and 52 weeks. Liver tumors occurred in significant numbers at 52 weeks only after NDMA/PCBs. At 72 weeks both tumor types had similar incidences in both NDMA-only and NDMA/PCB groups. The results confirm that PCBs promote lung as well as liver tumors by triggering the early appearance of latent, neonatally initiated tumors otherwise presenting in old age.
