Effect of dietary protein depletion and ethanol on demethylation and denitrosation of N-nitrosodimethylamine by rabbit liver microsomes.

To study how the metabolism of N-nitrosodimethylamine (NDMA) is affected by dietary protein level and chronic ethanol feeding, 24 rabbits at 18 weeks of age, assigned to four groups, each with 6 rabbits, were fed for 8 weeks on the following 4 different diets; 21% protein content containing 21.1% casein and water, 21% protein content containing 21.1% casein and 7.5% ethanol, 7% protein content containing 4.8% casein and water, 7% protein content containing 4.8% casein and 7.5% ethanol. Body weights, liver weights and microsomal protein contents in the liver were significantly smaller in 7% protein diet groups than in 21% protein diet groups. Microsomal P-450 contents per protein content were less in 7% protein diet groups than in 21% protein diet groups. NDMA demethylation activity due to non-arachidonic acid stimulated system (NASS) and NDMA denitrosation activity were greater in 21% protein diet groups than in 7% diet groups. Chronic ethanol feeding increased NDMA denitrosation activity due to arachidonic acid stimulated system in both dietary protein levels. The ratio of NDMA demethylation activity (carcinogenic action) to NDMA denitrosation activity (detoxication action) was greater in 7% dietary protein groups than 21% dietary protein groups. The value of this ratio was decreased by chronic ethanol feeding in 7% dietary protein groups. Cytotoxic and carcinogenic actions of NDMA might be enhanced by low protein diet due to inhibition of denitrosation of NDMA in liver microsome and chronic 7.5% ethanol feeding alleviates metabolic activation of NDMA to carcinogenic compounds.