N-nitrosodimethylamine blood levels in patients with chronic renal failure: modulation of levels by ethanol and ascorbic acid.
We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals. Five minutes after oral administration of ethanol (0.4 g/kg of body weight), all patients exhibited a significant (P less than .01) rise in blood NDMA levels (338 +/- 125 ng/kg), suggesting continuous endogenous formation of NDMA that was unmasked by ethanol's ability to inhibit first-pass hepatic metabolism of NDMA. In five of six patients, pretreatment with oral ascorbic acid resulted in a blunting, but not statistically significant, effect on maximum blood NDMA levels after consumption of ethanol. Mean levels were 340 +/- 100 ng/kg before treatment with ascorbic acid and 237 +/- 127 ng/kg during treatment. Ethanol administration unmasks increased gastrointestinal formation of NDMA in patients with chronic renal failure. Further studies are required to confirm a possible link between endogenous NDMA formation and the increased incidence of cancer in these patients.
Dunn
S R
SR
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Simenhoff
M L
ML
Lele
P S
PS
Goyal
S
S
Pensabene
J W
JW
Fiddler
W
W
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001205:Ascorbic Acid / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000431:Ethanol; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid