The mechanisms of intestinal absorption of the carcinogen MNNG (N-methyl-N'-nitro-N-nitrosoguanidine).
We studied the characteristics and mechanisms of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) intestinal absorption and the interaction between bile acids and fatty acids and MNNG absorption rate in vivo in male Sprague-Dawley rats. We perfused a segment of the proximal small bowel with a physiological solution containing MNNG to assess its basic kinetics and the influence of some physiological and dietary factors on carcinogen absorption. We found that MNNG was absorbed by simple passive diffusion. Transport of MNNG was the highest at pH 6.0. The addition of the bile salt, taurocholate by itself, greatly increased MNNG absorption, while the addition of the long-chain unsaturated fatty acids, oleic and linoleic, decreased the rate of absorption of MNNG. The phospholipid lecithin addition to the perfusate did not change the rate of MNNG absorption. Induction of dietary vitamin A deficiency (serum vitamin A level decreased from 40.9 to 13.7 micrograms/dl) did not change the absorption rate of MNNG. These studies demonstrate that bile acids, dietary fatty acids, and the pH of the intestinal content can modify the rate of absorption of this carcinogen by the small intestine. Since initial intestinal absorption determines serum levels and subsequent reabsorption and enterohepatic cycling determines long-term lumenal levels, serum levels, and total body content, factors which modify the rate of intestinal absorption of MNNG could also modify its carcinogenicity.
Koyama
S Y
SY
Department of Medicine, University of California, Irvine 92717.
Hollander
D
D
Dadufalza
V
V
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004058:Diffusion; D005227:Fatty Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000378:metabolism
D001647:Bile Acids and Salts; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008769:Methylnitronitrosoguanidine; D013656:Taurocholic Acid