Effect of genistein on DMBA-induced oral carcinogenesis in hamster

Genistein, an isoflavone present in soy at high concentrations and being considered the primary antitumor constituent in soy, has been known to be a natural anticancer agent in in vitro studies and experimental animal models. The present study was aimed to investigate the putative chemopreventive effect of genistein on oral carcinogenesis in hamster cheek pouch at the post-initiation stage, as well as its effect on angiogenesis during this process. DMBA solution (0.5% in mineral oil) was applied topically to the left cheek pouch of male Syrian golden hamsters three times a week for 6 weeks. Two days after the last treatment of DMBA, genistein suspended in distilled water (10 mg/kg body Wt/day) or same volume of distilled water was administered into the animals by gavage daily for 12 weeks. The genistein treatment decreased the visible oral tumor incidence to 40.7 (11/27) from 53.6% (15/28) of the positive control, but the difference was not statistically significant (P = 0.34). And no significant difference in the average number of tumors/tumor-bearing hamster, the average tumor volume, or latency was observed between the control and the genistein-treated group. Vascular density in OSCC of the genistein-treated group and that of the control group was similar and there was no significant difference. Importantly, three animals in the genistein-treated group produced poorly-differenciated fibrosarcomas in the DMBA-painted cheek pouches. The exact mechanism behind this needs further investigation. In conclusion, no inhibitory effect of genistein on chemically-induced post-initiation stage of oral carcinogenesis was observed in the present study. On the contrary, genistein appeared to promote oral submucosa stroma tumorigenesis in concert with DMBA. So caution should be warranted for people with predisposition to oral cancer.