Effects of a single dose of polychlorinated biphenyls to infant mice on N-nitrosodimethylamine-initiated lung and liver tumors.
Polychlorinated biphenyls (PCBs) are widespread, chemically-stable environmental contaminants; some congeners are commonly found in human adipose tissue and breast milk. We investigated the effects of a single dose of one PCB mixture (Aroclor 1254) on tumors initiated by N-nitrosodimethylamine (NDMA), also a common environmental agent. Infant outbred Swiss male mice were treated with NDMA (5 mg/kg) i.p. on the 4th day of life, to initiate lung and liver tumors. Four days later each received a single intragastric dose of PCBs (50, 250, or 500 mg/kg of Aroclor 1254) or oil. Groups were killed 16 and 28 weeks later. At both endpoints the mice given 500 mg/kg PCBs after NDMA developed twice as many lung tumors (alveologenic adenomas) as those treated with NDMA only, a significant difference. The PCBs alone did not cause lung tumors. This is the first demonstration of tumor promotion by PCBs in an extrahepatic organ, and it occurred after a single exposure. There were also complex, multiple effects on NDMA-caused liver tumors (adenomas and carcinomas) and on focal hepatocellular proliferative lesions: PCB treatment after the NDMA was associated with decreased number but increased size of these tumors and foci. All of these changes were accompanied by retention in the bodies of 0.1-6 ppm PCBs, as indicated by gas chromatography with electron capture detection. Of this, 80% or more consisted of 2,4,5,2',4',5'-and 2,3,4,2',4',5'-hexachlorobiphenyls in about equal amounts for periods up to 28 weeks. These results point to a need for both experimental and epidemiological studies of the effect of PCB body burden on tumor development.
D000818:Animals; D000831:Animals, Newborn; D001140:Aroclors / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D020111:Chlorodiphenyl (54% Chlorine); D002849:Chromatography, Gas; D003043:Cocarcinogenesis; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005306:Fertilization / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced; D012737:Sex Factors; D014018:Tissue Distribution
D001140:Aroclors; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; D004128:Dimethylnitrosamine