Phenobarbital and 3-methylcholanthrene treatment alters phase I and II enzymes and the sensitivity of the rat colon to the carcinogenic activity of azoxymethane.
It has been hypothesized that cancer risk may be influenced by phase I and II drug-metabolizing enzyme systems. This study attempted to determine the relationship between colon phase I and II enzyme activity and the subsequent induction of aberrant crypt foci (ACF), preneoplastic lesions by azoxymethane (AOM), a colon-specific carcinogen. Phenobarbital (PB) and 3-methylcholanthrene (MC) treatment (prototype hepatic inducers of phase I and II enzymes) provided the framework to study the induction of phase I and II enzymes in the rat colonic mucosa. Following induction for five consecutive days, the animals were given a single injection of AOM. Phase I and II enzymes were determined fluorometrically and spectrophotometrically and ACF were identified microscopically. Phase I and II xenobiotic metabolizing enzymes were induced in the rat colonic mucosa by prototype hepatic inducers. A lower number of ACF and crypt multiplicity was observed in animals induced with MC than in those in the non-induced and PB groups. Altered levels of phase I and II enzymes in the colon during preinitiation stages were associated with modulation in the growth of ACF, putative preneoplastic lesions.
Baijal
P K
PK
Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.
Fitzpatrick
D W
DW
Bird
R P
RP
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004790:Enzyme Induction; D018757:GABA Modulators / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D009245:NADH Dehydrogenase / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D018757:GABA Modulators; D008748:Methylcholanthrene; D009245:NADH Dehydrogenase; D005964:Glucosyltransferases; D005982:Glutathione Transferase; D001397:Azoxymethane; D010634:Phenobarbital