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Different Modifying Response of Butylated Hydroxyanisole, Butylated Hydroxytoluene, and Other Antioxidants in N,N-Dibutylnitrosamine Esophagus and Forestomach Carcinogenesis of Rats¹

First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan

The modifying effects of antioxidants were examined in a carcinogenesis system after N,N-dibutylnitrosamine treatment. Male F344 rats were given 0.05% N,N-dibutylnitrosamine in their drinking water for 4 wk and then treated with basal diet containing 2% butylated hydroxyanisole (BHA), 1% butylated hydroxytoluene (BHT) with 7 ppm vitamin K, 0.8% ethoxyquin, 5% sodium L-ascorbate, 5% sodium erythorbate, or no added chemical for 32 wk. BHA enhanced forestomach carcinogenesis but did not enhance esophageal carcinogenesis. BHT enhanced esophageal carcinogenesis but did not enhance forestomach carcinogenesis. Ethoxyquin significantly enhanced esophageal tumorigenesis. Neither esophageal nor forestomach carcinogenesis was affected by the other antioxidants evaluated. BHA significantly increased DNA synthesis of the forestomach epithelium, whereas BHT tended to increase that of the esophageal epithelium. Thus, BHA and BHT showed different modifying responses in carcinogenesis of the esophagus and forestomach.

¹ This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare of Japan, and by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10 Year Strategy for Cancer Control, Japan.

² To whom requests for reprints should be addressed, at the First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuhocho, Mizuho-ku, Nagoya 467, Japan.

Received 9/ 2/86. Revised 12/17/86. Accepted 1/15/87.