Existence of a Threshold for Induction of Aberrant Crypt Foci in the Rat Colon with Low Doses of 2-Amino-1-methyl-6-phenolimidazo[4,5-b]pyridine | Zendy

Shoji Fukushima | Zendy

Open Access

Existence of a Threshold for Induction of Aberrant Crypt Foci in the Rat Colon with Low Doses of 2-Amino-1-methyl-6-phenolimidazo[4,5-b]pyridine

Author(s) -

Shoji Fukushima

Publication year - 2004

Publication title -

toxicological sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.352

H-Index - 183

eISSN - 1096-6080

pISSN - 1096-0929

DOI - 10.1093/toxsci/kfh104

Subject(s) - aberrant crypt foci , carcinogen , chemistry , carcinogenesis , genotoxicity , deoxyguanosine , colorectal cancer , adduct , crypt , cancer , dna damage , pyridine , cancer research , dna adduct , dna , biochemistry , medicine , microbiology and biotechnology , biology , toxicity , gene , colonic disease , medicinal chemistry , organic chemistry

Until recently it has been generally considered that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the nonthreshold theory can be challenged with regard to assessment of cancer risk to humans. In the present study we show that a food derived, genotoxic hepatocarcinogen, 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine (PhIP), does not induce aberrant crypt foci (ACF) as preneoplastic lesions at low dose (below 50 ppm) or 8-hydroxy-2'-deoxyguanosine (below 400 ppm) in the rat colon. Moreover PhIP-DNA adducts were not formed at the lowest dose (below 0.01 ppm). Thus, the dose required to initiate ACF is approximately 5000 times higher than that needed for adduct formation. The results imply a no-observed effect level (existence of a threshold) for colon carcinogenesis by a genotoxic carcinogen.

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