Effect of molybdenum supplementation on N-nitroso-N-methylurea-induced mammary carcinogenesis and molybdenum excretion in rats

Abstract

Molybdenum (Mo) supplementation reduces the incidence of nitrosamine-induced tumors in the esophagus and forestomach of laboratory animals, and the incidence of mammary cancer in female rats induced by N-nitroso-N-methylurea (NMU). The present study was conducted to evaluate the effect of graded amounts of Mo on NMU-induced mammary carcinogenesis, and on the excretion of Mo and copper (Cu). Female Sprague-Dawley rats aged 5 wk were given ad libitum a low-Mo (0.026 mg/kg) diet and deionized water. After 15 d, a single SC injection of 50 mg NMU/kg body wt was administered to each of 30 rats in groups 2-5. Eight rats in group 1 served as untreated control. One week after the carcinogen treatment, 0.1, 1.0, or 10 mg Mo from sodium molybdate were added to each liter of drinking water for groups 3, 4, and 5, respectively. Groups 1 and 2 did not receive any Mo supplementation. After the rats had been Mo-supplemented for 38, 67, and 85 d, 48-h urine and fecal samples were collected from the same 48 rats, and Mo and Cu were determined. Molybdenum seemed to have little effect on Cu excretion. At each time interval, animals fed 0 or 0.1 mg Mo/L excreted more Mo in feces than in urine, whereas rats fed 1 and 10 mg Mo/L water excreted more Mo in urine than in feces, which indicates that Mo absorption was not easily saturated as the amount of Mo increased. However, the liver became saturated with Mo when 0.1-1 mg Mo/L was fed. The total number of palpable tumors per group 101 d after NMU administration was 109, 115, 101, and 81, and the total carcinomas per group were 92, 96, 86, and 65 for the animals in groups 2-5, respectively. The results indicate that supplemental Mo in the amount of 10 mg/L of drinking water inhibited mammary carcinogenesis.