COMPARISON OF TRANSPLACENTAL AND NEONATAL INITIATION OF MOUSE LUNG AND LIVER-TUMORS BY N-NITROSODIMETHYLAMINE (NDMA) AND 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK) AND PROMOTABILITY BY A POLYCHLORINATED-BIPHENYLS MIXTURE (AROCLOR 1254)

We have previously shown a positive tumor-promoting effect of a single dose of Aroclor 1254 on lung and liver tumors initiated neonatally in the mouse by N-nitrosodimethylamine (NDMA). In this study, we have co nfirmed and extended this observation with NDMA and the tobacco-specif ic nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) g iven either transplacentally or postnatally, followed by a single dose of Aroclor 1254 on day 56. This polychlorinated biphenyl (PCB) mixtur e was an effective promoter of both lung and liver tumors; however, th ere were specific initiator and sex-related differences in this respon se. Aroclor administration significantly increased the incidence of lu ng tumors initiated transplacentally by NDMA or NNK in male mice. Neit her nitrosamine initiated tumors transplacentally in females, but lung tumors initiated with NNK and liver tumors caused by NDMA in neonatal females were promoted by PCBs. Both liver and lung tumors initiated n eonatally by NDMA in male animals, but not NNK-initiated tumors, were promoted by PCBs. These data confirm that PCBs are able to promote bot h NDMA- and NNK-initiated tumors, but with chemical-, sex- and age-dep endent difference; this suggests influences of both quantitative and q ualitative factors in susceptibility to tumor promotion.