Increased numbers of N-nitrosodimethylamine-initiated lung tumors in mice by chronic co-administration of ethanol.
Young male strain A mice received 0.5, 1.0 or 5.0 p.p.m. N-nitrosodimethylamine (NDMA) in their drinking water with or without 10 or 20% ethanol. NDMA caused primary tumors of the lung in a dose-dependent manner; these were enumerated after 16 weeks. At the two lower NDMA doses, the ethanol caused a 1.5- to 3-fold increase in the number of lung tumor bearers and a 2-3.5 increase in lung tumor multiplicity. With 5 p.p.m. NDMA concomitant exposure to 10% ethanol resulted in a 2-3.5 increase in multiplicity. In a test for a possible tumor-promoting effect of the ethanol, mice were given 5 p.p.m. NDMA for 4 weeks, followed by ethanol for 12 weeks. There was an insignificant 30% increase in numbers of tumors. By contrast, mice that had received 10% ethanol along with NDMA during the initial 4 weeks experienced a 2.5-fold increase in incidence and 6-fold increase in multiplicity of lung tumors at 16 weeks. Thus, ethanol given simultaneously with chronic oral NDMA greatly enhances tumorigenesis in the lung, by a mechanism probably related to competitive inhibition of NDMA metabolism in the liver and not attributable to promotion of these tumors.
Anderson
L M
LM
Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRF, MD 21701.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000008:administration & dosage*; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000139:chemically induced*; D051379:Mice
D000431:Ethanol; D004128:Dimethylnitrosamine