Re: Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial.

Duffield-Lillico et al. (1) reported an increase in skin cancer for those taking selenium supplementation as a secondary prevention for nonmelanoma skin cancer in a randomized trial. Importantly, the National Cancer Institute (NCI) in the early 1980s evaluated selenium sulfide (SeS2, CAS No. 7446-34-6) and a shampoo formulation containing SeS2 (Selsun) for potential carcinogenicity in experimental animals (2– 4; Huff J: unpublished data). These were selected for study on the basis of widespread worker and consumer exposures. Selenium finds considerable and rising use as a nutritional additive to animal and human diets and in hair shampoos, and it is being evaluated for chemoprevention of human cancers. Four carcinogenesis bioassays were conducted via oral or dermal routes of exposure. SeS2 in 0.5% aqueous carboxymethylcellulose was given by oral intubation 7 days/ week for 2 years to Fischer rats at 0, 3, and 15 mg/kg per day and to B6C3F1 mice at 0, 20, and 100 mg/kg per day. Dermally, SeS2 in 0.5% aqueous carboxymethylcellulose was applied to the clipped backs of ICR Swiss mice at 0, 0.5, or 1.0 mg three times a week for 86 weeks. Likewise, Selsun shampoo (2.5% SeS2) was applied to ICR Swiss mice at 0.05 mL of a 25% (0.31 mg of SeS2) or a 50% (0.625 mg of SeS2) solution in distilled water three times per week. Oral exposure of SeS2 caused primarily liver tumors in male and female rats and liver and lung tumors in female mice. Male rats also exhibited increases in interstitial cell tumors of the testes and of the hematopoietic system (leukemias). Despite early deaths from amyloidosis and the limited lifespan of Swiss mice, dermal application of SeS2 was associated with tumors of the lung and circulatory system in female mice, and dermal exposure to SeS2 shampoo showed increases in lung tumors in male mice. In addition to causing skin cancers in humans (1), these experimental carcinogenic results (2–4; Huff J: unpublished data)—tumors of the liver, lung, and testes and the hematopoietic and circulatory systems—should caution us that long-term selenium intake may be more hazardous than previously realized. Thus, we should be equally concerned about and on the lookout for other potential cancer sites in humans in occupational settings as well as in those taking selenium-containing supplements. Notably however, Duffield-Lillico et al. (5) show a protective effect of selenium supplementation on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline prostatespecific antigen and plasma selenium concentrations. Additionally, beginning in mid 2001, the NCI began a large prostate cancer prevention trial with 32 000 men aged 55 years or older who will be taking neither, either, or both selenium and vitamin E (6), the premise being that selenium and vitamin E are both naturally occurring antioxidants capable of neutralizing free radicals that might otherwise damage genetic material and possibly lead to cancer. Perhaps during the NCI prostate cancer prevention trial using selenium and vitamin E, these men should be monitored closely for signs of cancer development as well as for gauging protective effects against prostate cancer. Meanwhile, prospective experimental long-term