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Effect of Selenium and Molybdenum on Methylbenzylnitrosamine-Induced Esophageal Lesions and Tissue Trace Metals in the Rat¹

Department of Preventive Medicine and Community Health ^* Department of Pathology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103

Thirty-six weanling male Sprague-Dawley rats were randomly assigned to one of four treatment groups: 1) SE rats received 4.0 ppm selenium as sodium selenite in drinking water containing 1% sucrose; 2) 15MO rats received 15 ppm molybdenum as sodium molybdate in the drinking water; 3) 45MO rats received 45 ppm molybdenum in their water; and 4) CON rats received distilled-deionized water containing only 1% sucrose. The esophageal carcinogen methylbenzylnitrosamine (MBN) was administered intragastrically in 10% ethanol twice per week for 5 wk at a dose of 2.5 mg/kg. MBN dosing was followed by a 12-wk period for tumor promotion. After this, heart, lungs, liver, spleen, kidneys, testes, tibia, muscle, brain and esophagus were excised. The esophagus was examined for MBN-induced lesions using dissecting and light microscopes and a portion was analyzed for Se. All other tissues were analyzed for Cu, Zn, Fe and Mn; some were also analyzed for Se and Mo. Most rats had precancerous lesions, and all rats had papillomas. There were no significant differences among the four treatment groups in the incidence and number per rat of precancerous lesions or gross papillomas. The SE group had significantly fewer carcinomas per rat than the other groups. The SE rats exhibited a number of significant differences in tissue trace element concentrations; in particular, they had higher Fe concentrations in heart, kidney and spleen than the other rats. The SE rats also had significantly greater urinary excretion of Mn and Fe, and excretion of the latter elements was significantly correlated with that of selenium. It is possible that the antitumor activity of Se is related to its effects of the metabolism of other essential trace elements.

KEY WORDS: • esophageal cancer • selenium • molybdenum • iron

¹ Supported by Grant #84-575-CCR from the New Jersey State Commission on Cancer Research.

Manuscript received 27 February 1986. Revision accepted 17 July 1986.