Long-term preventive regimen of tamoxifen and recombinant human interferon α2b on dimethylbenz (a) anthracene

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Recently, we have reported that recombinant human interferon alpha 2b (rHuIFN α2b) enhances the therapeutic efficacy of tamoxifen (TAM), an estrogen antagonist, against Ehrlich ascites carcinoma (EAC) in mice. We now present a long-term preventive regimen of TAM and rHuIFN α2b against chemically-induced estrogen-dependent mammary carcinoma. The experimental tumor was induced by single intragastric administration of dimethylbenz(a)anthracene (DMBA, 10 mg/rat) in virgin female albino rats (50 days old). The animals were fed a high fat diet (20% corn oil). Two months after the carcinogen administration, therapy was started. TAM (0.1 mg/rat), rHuIFN α2b (105 U/rat) and their combination were injected intraperitoneally twice weekly for 16 weeks. The antitumor preventive potential of the test drugs as well as their effects on animals growth rate, brain monoamines level, liver and kidney functions as well as adrenal gland pathology were evaluated. Our results indicate that administration of TAM along with rHuIFN α2b afforded a superior preventive regimen than either monotherapies regarding the yield of tumors (incidence and weight). Moreover, the combined drags produced a marked amelioration of the adrenal gland damage induced in mammary tumor-bearing groups. The animals growth rate as well as the liver and kidney functions were not significantly altered by the combined therapy as compared to TAM and rHuIFN α2b monotherapies. On the other hand, although the TAM/rHuIFN α2b therapy reduced the brain monoamines level, viz., 5-hydroxytryptamine, norepinephrine and dopamine as compared to control tumor-bearing group, no significant change was observed when compared to either monotherapies. The present study revealed that the combination of TAM with rHuIFN α2b confers a more beneficial chemopreventive regimen than either monotherapies against estrogen-dependent mammary carcinoma. Meanwhile, the combined drugs treatment does not add more burden than either monotherapies.

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