Preventive effect of MSM on mammary tumor at the initiation stage of hormonal carcinogenesis induced by 17b-estradiol (E2) in female ACI rats.

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Previous study indicated that MSM, an organic sulfur donor, was able to prevent cancer at the initiation stage of chemical carcinogenesis in female SD rats. It has a long history of use for a variety of health conditions including cancer. Sulfur from MSM was incorporated into methionine and cysteine after feeding ³²S-labeled MSM to guinea pigs. MSM in drinking water was able to prevent colon and mammary breast cancer in animals. In this study, we examined if MSM possessed a preventive effect on a mammary tumorigenic model induced by17β-estradiol (E2) at the initiation stage in female ACI rats. Forty-five, 5 week-old female ACI rats were divided into three groups, 15 rats each, and placed on regular chow. Age-matched control animals were supplied with regular drinking water only. 5% placebo and 5% MSM in drinking water were supplied to the animals till the 90th day after E2 pellet implantation, respectively. Two weeks after giving placebo and MSM, all animals were implanted subcutaneously with a 25 mg pellet containing 22.5 mg of E2 mixed with 2.5 mg cholesterol. The control animals received a 25 mg cholesterol pellet implant. The animals in the placebo group had significant body weight loss when compared to the age-matched control group. The animals in the MSM group had slight body weight loss and none of the rats implanted with cholesterol pellets exhibited enlarged mammary glands. All rats with an E2 implant in the placebo group showed enlarged mammary glands. One hundred percent of the rats in the placebo group had 3 to 7 enlarged mammary glands. 57% of the rats in the MSM group had 1 to 4 enlarged mammary glands. The average enlarged mammary gland area in the placebo group and MSM group at 160 days after E2 implantation was 17 and 10 mm², respectively. The survival rates of the control, 5% placebo, and 5% MSM at 160 days after E2 implantation were 100%, 0.00%, and 73%, respectively. The survival rate of different groups at 180 days was 100%, 0.00%, and 20%, respectively. The behaviors and overall health conditions between groups were significantly different. The animals in the control group were normal and healthy. The animals in the placebo plus E2 group were lethargic and thin. The animals in the E2 plus MSM group were much more active and healthier than that in the placebo plus E2 group. It is the first finding that MSM is able to prevent pre-cancerous activity in estrogen-induced mammary tumors in female ACI rats. The enlarged mammary glands in different groups showed mammary gland proliferation and cystic lesions. Since toxicity of E2 in ACI rats was observed, animals died in an early time after E2 implantation. Therefore, the dose of E2 should be decreased in ACI rats for a tumor induction and preventive study. Consequently it was suggested that a 5 - 10 mg of E2 pellet implant per rat might be the optimal dose for studies of hormonal carcinogenesis and cancer prevention.