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).

Abstract

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 confirmed and extended this observation with NDMA and the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) given either transplacentally or postnatally, followed by a single dose of Aroclor 1254 on day 56. This polychlorinated biphenyl (PCB) mixture was an effective promoter of both lung and liver tumors; however, there were specific initiator and sex-related differences in this response. Aroclor administration significantly increased the incidence of lung tumors initiated transplacentally by NDMA or NNK in male mice. Neither 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 neonatally by NDMA in male animals, but not NNK-initiated tumors, were promoted by PCBs. These data confirm that PCBs are able to promote both NDMA- and NNK-initiated tumors, but with chemical-, sex- and age-dependent difference; this suggests influences of both quantitative and qualitative factors in susceptibility to tumor promotion.