Tamoxifen Experimental Carcinogenicity Studies: Implications for Human Effects

Abstract

Conclusion

Tamoxifen is clearly DNA-reactive and carcinogenic in rat liver. Since most human carcinogens are DNA-reactive carcinogens in rodents (20), such findings with tamoxifen raise grave concern. The observations that tamoxifen is also DNA-reactive in hamster liver and is activated by human liver microsomes to form DNA adducts provide evidence that its toxicity is not confined to the rat. Accordingly, tamoxifen must be presumed to be a human cancer hazard, unless some mechanistic basis for nonsusceptibility of humans is discovered. The presumption of hazard is reinforced by the finding of p53 mutations in the tamoxifen-induced liver tumors. The p53 gene is the most commonly mutated gene in human neoplasms (21, 22).

Accordingly, we have recommended that women being given tamoxifen should be carefully monitored for carcinogenic effects (23–25). It is important in this regard to recognize that the target site for human carcinogens is not always the same as in rodents (20).