Mechanistic approach of contrasting modifying effects of caffeine on carcinogenesis in the rat colon and mammary gland induced with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
Caffeine exerts potent chemopreventive action against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary gland carcinogenesis, but acts as a co-carcinogen in the colon. The present work was performed to clarify mechanisms underling these organ dependent actions. Female F344 rats were given PhIP and caffeine, PhIP alone, caffeine alone or no treatment for 4 weeks. PhIP-DNA adduct formation in the colon was significantly higher in the PhIP+caffeine than in the PhIP group, but levels in the mammary glands showed no inter-group differences. CYP1A2 mRNA expression in the livers of the PhIP+caffeine group tended to be higher than in either the PhIP or the caffeine alone groups. High mRNA expression for both N-acetyltransferase (NAT) 1 and NAT2 was observed in the colon, with less expression in the mammary gland. The levels of four DNA-repair enzymes were not influenced by the caffeine treatment. In conclusion, only increased level of DNA adducts in the colon partially related to the modifying effects of caffeine on PhIP-induced rat carcinogenesis. Thus, other unknown factors must be contributory.
Takeshita
Fumitaka
F
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. taisho@med.nagoya-cu.ac.jp
Ogawa
Kumiko
K
Asamoto
Makoto
M
Shirai
Tomoyuki
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001940:Breast / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002273:Carcinogens; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis; D018736:DNA Adducts / Q000378:metabolism; D004260:DNA Repair; D004277:DNA, Single-Stranded; D005260:Female; D007093:Imidazoles; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D002273:Carcinogens; D000697:Central Nervous System Stimulants; D018736:DNA Adducts; D004277:DNA, Single-Stranded; D007093:Imidazoles; D012333:RNA, Messenger; D002110:Caffeine; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; D001973:Bromodeoxyuridine