Initiating activity of quinones in the two-stage transformation of BALB/3T3 cells.

2-tert-Butyl-1,4-benzoquinone (BQ), a metabolite of the rodent carcinogen 3-tert-butyl-4-hydroxyanisole (3-BHA), has been shown previously to have initiating activity for cell transformation. In this paper, we examined the initiating activity of quinones in a two-stage transformation assay using BALB/3T3 cells. Cells were treated first with a quinone and then with the tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA). The quinones tested were 1,4-benzoquinone (pQ), phenyl-1,4-benzoquinone (PhQ), menadione and 2,5-di-tert-butyl-1,4-benzoquinone (DBQ) in addition to BQ. pQ is a metabolite of benzene and phenacetin, and PhQ is a metabolite of o-phenylphenol (OPP) and sodium o-phenylphenate (OPP-Na). All of the tested quinones induced transformation in the presence of TPA but not in its absence. The extent of transformation caused by quinones followed by TPA was weak but statistically significant. Thus these quinones were shown to act as initiators in the transformation of BALB/3T3 cells. This result suggests that BQ, pQ and PhQ may be involved in carcinogenesis by 3-BHA, benzene, phenacetin, OPP and OPP-Na in vivo. Menadione has been reported to cause cytotoxic effects and mutations through active oxygen generation from semiquinone radicals. DBQ has two bulky substitutes which interfere with covalent bonds with DNA. Menadione and DBQ exhibited initiating activity in the present study. This result suggests that active oxygens generated from semiquinone radicals may play a role in the initiation of cell transformation.