Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model

The effects of cacao liquor proanthocyanidins (CLPr) on tumorigenesis were investigated using a multi-organ carcinogenesis model in male F344 rats receiving combined treatment with a single i.p. injection of diethylnitrosamine (100 mg/kg body wt), four i.p. injections of N-methylnitrosourea (20 mg/kg body wt), four s.c. injections of dimethylhydrazine (40 mg/kg body wt), along with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine and then 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine, both in the drinking water, for 2 weeks each, during the initial 4-week period (DMBDD treatment). Starting 1 week thereafter, rats were administered CLPr at a dose of 0.025% or 0.25% and the experiment was terminated at week 36. The final survival rate for the DMBDD+0.25% CLPr group was significantly greater than for the DMBDD alone group. In the lung, significant reduction in the incidence and multiplicity of carcinomas was also observed, and in the thyroid, quantitative values for adenomas also tended to decrease in a CLPr dose-dependent manner. No significant modification in the small intestine, colon or kidney was evident. These results indicate that CLPr exerts chemopreventive effects in the lung without any promoting influence in other major organs.