Initiating activity of 3-tert-butyl-4-hydroxyanisole (3-BHA) and its metabolites in two-stage transformation of BALB/3T3 cells.
3-tert-Butyl-4-hydroxyanisole (3-BHA) and its metabolites, tert-butyl-1,4-benzoquinone (BQ) and 3-tert-butyl-5-methoxy-1,2-benzoquinone (BHAoQ), were tested for initiating activity in a two-stage transformation assay using BALB/3T3 cells. Cells were treated first with a test chemical and then with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). In the absence of TPA the test chemicals did not induce cell transformation. With the promoting treatment, 3-BHA and BQ induced dose-dependent cell transformation. There were statistically significant increases in the proportion of dishes with transformed foci in the cultures treated with 30 micrograms/ml 3-BHA plus TPA (15 of 24 dishes, P less than 0.005) and with 0.4 microgram/ml BQ plus TPA (12 of 22 dishes, P less than 0.02) as compared to the cultures treated with DMSO plus TPA (5 of 24 dishes). BHAoQ caused a non-significant increase in transformation frequency in the presence of TPA. In conclusion, 3-BHA and BQ had an initiating activity in the cell transformation system and the potency of BQ was approximately 100 times higher than that of 3-BHA.
Sakai
A
A
Division of Microbiology, National Institute of Hygienic Sciences, Tokyo, Japan.
Miyata
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N
Takahashi
A
A
D000818:Animals; D016227:Benzoquinones / Q000633:toxicity*; D002083:Butylated Hydroxyanisole / Q000633:toxicity* / Q000031:analogs & derivatives; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D051379:Mice; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D016227:Benzoquinones; D002083:Butylated Hydroxyanisole; C066449:3-tert-butyl-5-methoxy-1,2-benzoquinone; C051362:3-tert-butyl-4-hydroxyanisole; C051290:2-tert-butyl-4-quinone; C044874:3-tert-butyl-4,5-dihydroxyanisole; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide