Table 1.

In vivo animal studies that assessed prostate cancer prevention by selenium.

Animal Model [Ref.]	Agent and Dose	Results
Studies relevant to SELECT trial design
N-Nitroso-N-methylurea (MNU) + testosterone-treated Wistar-Unilever rats [42]	l-selenomethionine (1.5 or 3 mg/kg diet) dl-α-tocopherol (4000 or 2000 mg/kg diet) l-selenomethionine ( 3 mg/kg diet ) + dl-α-tocopherol (2000 or 5000 mg/kg diet) Selenized yeast (target Se levels of 9 or 3 mg/kg diet) Control	No effect on prostate cancer incidence in any group
Testosterone + estradiol-treated NBL rat [43]	l-selenomethionine (1.5 or 3.0 mg/kg diet) dl-α-tocopherol (4000 or 2000 mg/kg diet) Control	No effect on prostate tumor incidence, multiplicity, or death in any group
Studies on selenium in combination with other agents only
Lady transgenic mice [44]	α-tocopherol succinate (800 IU) + l-selenomethionine (200 μg) + lycopene (50 mg) α-tocopherol succinate (800 IU) + l-selenomethionine (200 μg) Control	Increased survival ( p < 0.0001) in both treatment groups compared to control, no effect on prostate tumor incidence in any group
Lady transgenic mice [45]	α-tocopherol succinate (800 IU) + l-selenomethionine (200 μg) + lycopene (50 mg) Control	Four-fold decrease in prostate cancer incidence in animals treated with 3 agents combined compared to control animals ( p < 0.0001)
Studies on other forms of selenium
Transgenic adenocarcinoma mouse prostate (TRAMP) model [46]	Methylseleninic acid (3 mg selenium/kg body weight) for 10 weeks Methylseleninic acid (3 mg selenium/kg body weight) for 16 weeks Control	Decreased cancer-specific mortality in methylseleninic acid groups compared to control group ( p10 weeks = 0.0078, p16 weeks = 0.0385)
MNU + testosterone-treated Wistar rats [47]	Sodium selenite (4 mg/L in drinking water/day) Control	No effect on prostate intraepithelial neoplasia, decreased prostate cancer multiplicity by 44.6% in sodium selenite group compared to control group