TY - JOUR
T1 - 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
AU - Fukushima, S.
AU - Wanibuchi, H.
AU - Morimura, K.
AU - Iwai, S.
AU - Nakae, D.
AU - Kishida, H.
AU - Tsuda, H.
AU - Uehara, N.
AU - Imaida, K.
AU - Shirai, T.
AU - Tatematsu, M.
AU - Tsukamoto, T.
AU - Hirose, M.
AU - Furukawa, F.
N1 - Funding Information:
The authors would also like to acknowledge the encouragement of Dr. N. Ito (Emeritus Prof., Nagoya City University Medical School, Nagoya) and Dr. T. Kitagawa (Director, Cancer Institute, Tokyo). This research was supported by a grant from the Japan Science and Technology Corporation, included in the Project of Core Research for Evolutional Science and Technology (CREST) and a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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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U2 - 10.1093/toxsci/kfh104
DO - 10.1093/toxsci/kfh104
M3 - Article
C2 - 15014208
AN - SCOPUS:3242812054
SN - 1096-6080
VL - 80
SP - 109
EP - 114
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -
