Association between acetylator genotype and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) DNA adduct formation in colon and prostate of inbred Fischer 344 and Wistar Kyoto rats.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine (HCA) found in cooked meats, causes colon and prostate tumors in male rats. Polymorphic N-acetyltransferase metabolizes N-hydroxy-PhIP to a DNA-reactive form. Liver, colon, and prostate PhIP-DNA adduct levels were compared in male rapid-acetylator Fischer 344 (F344) and slow-acetylator Wistar-Kyoto (WKY) rats fed 0.01 or 0.04% PhIP. Liver PhIP-DNA adduct levels at both PhIP doses, and colon PhIP-DNA adduct levels at the 0.01% PhIP dose were unaffected by acetylator genotype. However, in rats fed 0.04% PhIP, colon PhIP-DNA adduct levels were higher in rapid acetylator F344 rats (P < 0.05). Similarly, prostate PhIP-DNA adduct levels were higher in rapid acetylator F344 rats at both PhIP doses (P < 0.05). The combination of the high-PhIP dose and rapid-acetylator genotype resulted in the highest level of PhIP-DNA adducts in rat colon and prostate.
Purewal
M
M
Department of Gastrointestinal Medical Oncology and Digestive Diseases, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
Fretland
A J
AJ
Schut
H A
HA
Hein
D W
DW
Wargovich
M J
MJ
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage*; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D013045:Species Specificity
D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine