Modulation of benzo[a]pyrene-induced morphological transformation of Syrian hamster embryo cells by butylated hydroxytoluene and butylated hydroxyanisole.

The Syrian hamster embryo cell transformation assay has been used to investigate the effect of two synthetic antioxidants on morphological transformation induced by the initiator benzo[a]pyrene (BP). A two-stage protocol was employed with an initiation phase of 2 days and a subsequent promotion phase of 5 days. When 10 microM butylated hydroxytoluene (BHT) were present in the promotion phase instead of the solvent the transformation frequency at 0.1 micrograms BP/ml increased from 0.27% to 0.55%; at 100 microM of BHT the transformation frequency was 0.77%. Butylated hydroxyanisole (BHA) also enhanced the percentage of transformed colonies from 0.40% (10 microM) to 0.49% (100 microM), respectively. No significant initiating activity was detected for both antioxidants when tested in the initiation phase instead of BP; when the antioxidants were applied simultaneously with BP (1 microgram/ml) during the initiation phase the transformation frequency was decreased from 0.64% to 0.15% (100 microM BHT) and to 0.17% (100 microM BHA), respectively. These results show that the dual action of phenolic antioxidants on chemical carcinogenesis, which depends on the administration schedule, can be imitated in an in vitro test system. In addition to their anti-initiation effect, BHT and BHA, while devoid of intrinsic initiator potency, exert a moderate promotional activity on hamster embryo cell cultures. Their ability to enhance tumorigenesis by various carcinogens in vivo is likely to be at least partially related to such promotion-like effects on cell growth and morphology.