Sakai A, Miyata N, Takahashi A
Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
Carcinogenesis. 1995 Mar;16(3):477-81. doi: 10.1093/carcin/16.3.477.
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.
2-叔丁基-1,4-苯醌（BQ）是啮齿动物致癌物3-叔丁基-4-羟基茴香醚（3-BHA）的一种代谢产物，先前已证明其具有细胞转化启动活性。在本文中，我们在使用BALB/3T3细胞的两阶段转化试验中检测了醌类的启动活性。细胞首先用一种醌处理，然后用肿瘤促进剂12-O-十四烷酰佛波醇-13-乙酸酯（TPA）处理。除BQ外，所测试的醌类还有1,4-苯醌（pQ）、苯基-1,4-苯醌（PhQ）、甲萘醌和2,5-二叔丁基-1,4-苯醌（DBQ）。pQ是苯和非那西丁的代谢产物，PhQ是邻苯基苯酚（OPP）和邻苯基苯酚钠（OPP-Na）的代谢产物。所有测试的醌类在TPA存在时均能诱导转化，但在其不存在时则不能。醌类随后用TPA处理所引起的转化程度较弱，但具有统计学意义。因此，这些醌类在BALB/3T3细胞转化中表现为启动剂。该结果表明，BQ、pQ和PhQ可能在体内参与3-BHA、苯、非那西丁、OPP和OPP-Na的致癌作用。据报道，甲萘醌通过半醌自由基产生活性氧而引起细胞毒性作用和突变。DBQ有两个庞大的取代基，会干扰与DNA的共价键。甲萘醌和DBQ在本研究中表现出启动活性。该结果表明，半醌自由基产生活性氧可能在细胞转化启动中起作用。
