DNA adduct levels and intestinal lesions in congenic rapid and slow acetylator syrian hamsters admi food mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).
Epidemiological studies indicate that rapid acetylators with a high intake of well-done red meat have an increased risk of colorectal cancer. Arylamine N-acetyltransferase enzymes (E.C. 2.3.1.5) activate carcinogenic heterocyclic amines found in the crust of fried meat via O-acetylation of their N-hydroxylamines to reactive intermediates that bind covalently to DNA and produce mutations. Syrian hamsters as well as humans express two N-acetyltransferase isozymes (NAT1 and NAT2) which differ in substrate specificity and genetic control. Nucleic acid substitutions in the NAT2 gene segregate individuals into rapid, intermediate and slow acetylator phenotypes. In the present paper, we examined the role of the polymorphic NAT2 acetylator genotype in carcinogenesis induced by the food mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by comparing Syrian hamster lines congenic at the NAT2 locus. No differences were found between rapid and slow acetylator congenic hamsters in levels of intestinal PhIP-DNA adducts. In contrast to previous studies in rats, no carcinogen-related induction of the preneoplastic lesions aberrant crypt foci or tumors was found in the intestines of rapid and slow acetylator congenic Syrian hamsters administered PhIP or IQ.
Steffensen
I L
IL
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway. inger-lise.steffensen@folkhelsa.no
Fretland
A J
AJ
Paulsen
J E
JE
Feng
Y
Y
Eide
T J
TJ
Devanaboyina
U S
US
Hein
D W
DW
Alexander
J
J
D000107:Acetylation; D000236:Adenoma / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D020296:Animals, Congenic; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D018736:DNA Adducts / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D005502:Food; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D009153:Mutagens / Q000008:administration & dosage / Q000378:metabolism*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D011804:Quinolines / Q000008:administration & dosage / Q000378:metabolism*
D018736:DNA Adducts; D004273:DNA, Neoplasm; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D001191:Arylamine N-Acetyltransferase