Increased numbers of N-nitrosodimethylamine-initiated lung tumors in mice by chronic co-administration of ethanol

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Abstract
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 chronk oral NDMA greatly enhances tumorigenesis in the lung, by a mechanism Probably related to competitive inhibition of NDMA metabolisam in the liver and not attributable to promotion of these tumors.

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