Heterocyclic amine mixture carcinogenesis and its enhancement by caffeine in F344 rats

Citation
H. Tsuda et al., Heterocyclic amine mixture carcinogenesis and its enhancement by caffeine in F344 rats, CANCER LETT, 143(2), 1999, pp. 229-234
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER LETTERS
ISSN journal
0304-3835 → ACNP
Volume
143
Issue
2
Year of publication
1999
Pages
229 - 234
Database
ISI
SICI code
0304-3835(19990901)143:2<229:HAMCAI>2.0.ZU;2-C
Abstract
In order to elucidate whether mixed exposure to environmental carcinogens a nd caffeine increases the risk of cancer induction, we investigated the rel ationship between preneoplastic lesion development in the liver and colon a nd drug metabolizing enzyme induction and DNA adduct formation, in rats tre ated with a mixture of heterocyclic amines (HCAs) and caffeine. In Experime nt I, male F344 rats were administered 3 different HCAs, the food carcinoge ns, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimida zo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]py ridine (PhIP), alone or in combinations of 2 or 3 at 50 ppm in the diet for 16 weeks. The numbers of hepatic glutathione-S-transferase P form positive (GST-P+) foci and colonic aberrant crypt foci (ACF) were greater in the IQ + MeIQx group than expected from simple summation and increased levels of HCA-DNA adducts were noted. However, no summation was obtained when combine d with PhIP, which rather caused inhibition. In Experiment 2, the effects o f concurrent caffeine administration on the PhIP carcinogenicity were asses sed. Caffeine at 1000 and 500 ppm in the drinking water for 2 weeks signifi cantly increased levels of CYP1A2. Ten weeks concurrent administration of c affeine (1000 ppm) and PhIP (400 ppm) resulted in significant increase of c olon ACFs and CYP1A2 expression. Thus, concurrent administration of IQ and MeIQx caused elevation of their carcinogenicity but other mixtures with PhI P did not enhance carcinogenicity. However, a noncarcinogen, caffeine, enha nced PhIP colon carcinogenesis, possibly due to induction of CYP1A2. (C) 19 99 Elsevier Science Ireland Ltd. All rights reserved.