PROMOTION BY POLYCHLORINATED-BIPHENYLS OF LUNG AND LIVER-TUMORS IN MICE

Polychlorinated biphenyls (PCB), which are tumor promoters, have been found in human tissues for decades. Their contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion. Epidemiological associations have been see n between PCB exposure or tissue content and cancer at several sites. In rodents, tumor promotion by PCBs has been little studied in tissues other than liver. Previously, in an experiment modeling infant carcin ogen exposure following PCBs received in milk, lung and liver tumors, initiated neonatally in mice by the environmental nitrosamine N-nitros odimethylamine (NDMA), were promoted by later treatment with Aroclor 1 254. The present study was undertaken to confirm and characterize the effects of Aroclor 1254 on tumor number, latency, size and malignancy. Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 ( 250 mg/kg) on day 8, and killed at intervals. Eight PCB congeners were quantified in the carcasses. Incidences of mice with NDMA-initiated l ung tumors at 28 weeks of age were increased 2.5-fold by PCBs. Multipl icities of lung tumors were enhanced four-fold by PCBs at 28 and 52 we eks. By 72 weeks tumor numbers were similar in the NDMA-only and NDMA- PCB groups. Liver tumors first occurred in significant numbers at 52 w eeks and only in mice receiving both NDMA and PCBs. As for the lung, a t 72 weeks the incidence was high in both the NDMA-only and NDMA -PCB groups. Sizes of tumors and liver carcinoma incidence were not altered by PCB treatment. Carcass analysis revealed a significant positive as sociation between lung tumor numbers at 28 weeks and relative percenta ge of 2,2',4,4',5-pentachlorobiphenyl, with no other correlations. The results confirm that PCBs promote lung as well as liver tumors, by tr iggering the early appearance of latent initiated tumors otherwise pre senting in old age.