Genetic analysis of the susceptibility in rats to aberrant crypt foci formation by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine, PhIP.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine produced while cooking fish and meat, induces aberrant crypt foci (ACF) and colon cancers in rats. We previously reported that F344 rats were sensitive and ACI rats resistant to ACF formation by PhIP, and that the genetic susceptibility in F344 rats to ACF formation by PhIP was autosomally dominant over ACI rats. To identify candidate susceptibility genes in F344 rats, a preliminary genome-wide linkage analysis was employed using a subset of 170 progeny of (F344 x ACI)F1 x ACI backcross rats with either high or low sensitivity to ACF formation by PhIP. Three chromosomes, 1, 6 and 16, demonstrated the presence of loci with a logarithm of the odds (lod) scores of more than 1.0, and a susceptible gene for ACF formation by PhIP was suggested to reside on chromosomes 16.
Nakagama
H
H
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Souda
K
K
Ochiai
M
M
Ishiguro
Y
Y
Sugimura
T
T
Nagao
M
M
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000473:pathology*; D003108:Colonic Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D007093:Imidazoles / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344
D002273:Carcinogens; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine