Post-initiation effects of chlorophyllin and indole-3-carbinol in rats given 1,2-dimethylhydrazine or 2-amino-3-methylimidazo[4,5-f]quinoline

Chlorophyllin (CHL) is a water-soluble derivative of chlorophyll, the ubiqu itous pigment in green and leafy vegetables, whereas indole-3-carbinol (I3C ) is present in cruciferous vegetables such as cabbage, broccoli and caulif lower. In rats initiated with 1,2-dimethylhydrazine (DMH), CHL and I3C repo rtedly promoted or enhanced the incidence of colon tumors when they were ad ministered after, or during and after the carcinogen exposure, respectively . The same compounds given post-initiation inhibited the formation of colon ic aberrant crypts induced by heterocyclic amines, such as 2-amino-3-methyl imidazo[4,5-f]quinoline (IQ), but tumor suppression was not examined in the latter studies, In the present investigation, male F344 rats were treated, vith IQ or DMH during the first 5 weeks of a 1 year study; IQ was given in the diet (0.03%), whereas DMH was administered once a week by s.c. injectio n (20 mg/kg body wt). Beginning 1 week after the last dose of IQ or DMH unt il sacrifice, rats received 0.001, 0.01 or 0.1% (w/v) CHL in the drinking w ater or 0.001, 0.01 or 0.1% I3C in the diet. Compared with controls given c arcinogen alone, 0.1% I3C treatment suppressed the multiplicity of IQ-induc ed colon tumors, and CHL inhibited in a dose-related manner the incidence o f IQ-induced liver tumors, However, 0.001% CHL increased significantly the multiplicity of DMH-induced colon tumors while having no effect on the colo n tumors induced by IQ, These results indicate that both the choice of carc inogen as well as the dose of the tumor modulator can be important determin ants of the events that occur during post-initiation exposure to CHL or I3C , Based on the present findings and data in the literature, it is possible for CHL and I3C to act as tumor promoters or anticarcinogens, depending upo n the test species, initiating agent and exposure protocol.