Modifying effects of chitin, chitosan and their related compounds on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in a rat medium-term hepatocarcinogenesis model, and their post-initiation effects in a female rat 2-stage multi-organ carcinogenesis model.
The modifying effects of chitin, chitosan, chitin-oligo sugar, chitosan-oligo sugar and chlorophyllin-chitosan on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated in a rat medium-term hepatocarcinogenesis model. Male F344 rats were injected with diethylnitrosamine (DEN) and starting 2 weeks later, received 0.03% MeIQx alone, MeIQx plus each chemical (0.4%), or each chemical alone (0.1%) in diet for 6 weeks. Three weeks after the DEN injection, animals were subjected to 2/3 partial hepatectomy. The numbers and areas of glutathione S-transferase placental form (GST-P) positive foci given MeIQx plus test chemicals were similar to the MeIQx alone values. In a second experiment, post-initiation effects of chitin and chitosan on major organs were examined in female F344 rats after initiation with 1,2-dimethylhydrazine (DMH), 7,12-dimethylbenz[a]anthracene (DMBA) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN). In rats fed a diet containing 1.0% chitin for 36 weeks, the development of palpable mammary tumors tended to be delayed and the final incidence and multiplicity of adenocarcinomas, were significantly lowered. However, in the colon, the number of aberrant crypt foci (ACF) in the chitin and chitosan groups was significantly increased. These results indicate that chitin, chitosan and related compounds do not exert unequivocal chemopreventive effects on heterocyclic amine-induced hepatocarcinogenesis, and that effects in other organs may be tissue specific with possible inhibitory action in the mammary gland being offset by promotion of colon lesion development.
Kawabe
Mayumi
M
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. kawabe@dims.co.jp
Futakuchi
Mitsuru
M
Tamano
Seiko
S
Shirai
Tomoyuki
T
Hirose
Masao
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002686:Chitin / Q000494:pharmacology*; D048271:Chitosan / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D011810:Quinoxalines / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D011810:Quinoxalines; D002686:Chitin; D004052:Diethylnitrosamine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D048271:Chitosan; D005979:Glutathione Peroxidase