Selective Protective Effect of Butylated Hydroxytoluene Against 1,2-Dimethylhydrazine Carcinogenesis in BALB/c Mice2

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Abstract
The effect of the antioxidant butylated hydroxytoluene (BHT) was determined in 1,2-dimethylhydrazine (DMH) colon carcinogenesis. The following groups were comprised of female and male BALB/c mice that were either 1) given BHT (0.75% in the feed) for life beginning at 8 weeks of age, 2) inoculated with DMH (20 mg/kg body wt) sc for 10 weeks beginning at 11 weeks of age, 3) treated with BHT plus DMH, or 4) maintained as untreated controls. Mice of both sexes treated with BHT plus DMH had increased survival over those given DMH alone (females: 93 vs. 64%, P = 0.011; males: 92 vs. 57%, PP=0.0036), but not in females (60 vs. 50%). The numbers of tumors per tumor-bearing mouse were reduced in both sexes given BHT plus DMH as compared with mice given DMH alone (≈2.0 to ≈1.0). Neither BHT-treated mice nor untreated controls had colon or rectal tumors. DMH induced lung tumors, but BHT did not; tumor incidences in mice treated with BHT plus DMH were intermediate between those in mice given DMH or BHT alone. The sex-specific protective effect of BHT on the survival of mice treated with DMH and on the tumor incidences in the large bowel (males only) resembled the sex-specific effect of BHT on diethylnitrosamine-induced squamous cell tumors of the forestomach (females only), but the mechanisms remain unexplained and may be quite different.