Possible carcinogenic risks of copper gluconate and their prevention by co-administered green tea catechins evaluated by a rat medium-term multi-organ carcinogenicity bioassay protocol

Carcinogenic risks of copper gluconate, green tea catechins and their combined exposure were evaluated using a rat medium-term multi-organ carcinogenicity bioassay protocol. Male BrlHan:WIST@Jcl (GALAS) rats were given N-nitrosodiethylamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2′-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). Rats were then given a diet containing copper gluconate at a concentration of 0, 10, 300, 3000 or 6000 ppm with or without a co-administration of catechins starting 1 week later by admixing in the drinking water at a concentration of 5000 ppm. All survivors were sacrificed at the end of week 29. Number of putatively preneoplastic, glutathione S-transferase placental form-positive, liver lesions significantly increased by copper gluconate of 300 ppm or greater. In addition, both incidence and grade of hyperplasia in the forestomach significantly increased by copper gluconate of 6000 ppm. Catechins, exerting no effects by themselves, inhibited these effects of copper gluconate. The present results indicate that copper gluconate may possess carcinogenic risks for the liver and forestomach at its high dose level, and that co-administered green tea catechins may exert preventive effects.