Cancer Chemopreventive Action And Its Mechanism Of Action Of A Third-Generation Retinoid R8605

R8605 chemically is N-(4'-carboxyphenyl)-4-hydroxy-3,5-di-t-butyl benzamide. it belongs to the third-generation compound of retinoids and was found during the systematic screening of chemopreventive agents in our Institute. Previous studies have demonstrated that it is a good differentiation-inducer of human promyelocytic leukemia cells (HL-60) in vitro. Based on the theory of multistage carcinogenesis, We have studied the cancer chemopreventive effects of R8605 and its possible mechanism. Preliminary toxicity of H8605 was also studied in this paper.Experiments have proved that R8605 given either orally or topically significantly inhibited the growth of skin papillomas induced by 7,12-dimethylbenz(a)anthracene(DMBA) and croton oil in mice. The experimental results also indicated that it exhibited both anti-promoting and anti-initiating effects, but anti-promotion was its major action.R8605 administered orally at doses of 50 and 100mg/kg inhibited DMBA or cyclophosphomide-induced micronucleus formation in mice; it has no mutagenicity. On the contrary,- it selectively lowered the His+ revertants of TA 102 strain induced by BDS, carboplatin and mitomycin C in Ames test; It did not affect hepatic drug metabolizing enzymes including cytochrome P-450, NADPH-cytochrome C reductase and glutathione S-transferase in mice when given orally at dosages of 100 and 150mg/kg ,once daily for 4 days. These results suggested that the anti-initiating action of R8605 was related to its protection against DNA damage but not correlated with influencing carcingen activation or detoxification.