Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1993-03-01

Cytotoxic and genotoxic properties of tert.-butyl-p-quinone (TBQ) in an in vitro assay system with Chinese hamster V79 cells and in strain D7 of Saccharomyces cerevisiae.

C G Rogers, B G Boyes, T I Matula, G Neville, R Stapley

Index: Mutat. Res. 299(1) , 9-18, (1993)

Full Text: HTML

Abstract

tert.-Butyl-p-quinone (TBQ), a major metabolite of the phenolic antioxidant tert.-butyl-4-hydroxyanisole (BHA), was examined for cytotoxic and genotoxic properties in an in vitro assay system with Chinese hamster V79 cells and in diploid strain D7 of Saccharomyces cerevisiae. TBQ was prepared from BHA by oxidative demethylation with sodium nitrite at low pH. Spectroscopic analyses identified the crystalline reaction product as TBQ with a purity close to 100%. Cytotoxicity of TBQ was determined by cloning efficiency in the absence of hepatocyte activation. TBQ reduced colony size of V79 cells at 0.4 micrograms/ml, prevented growth of 50% of the cells at 0.6 micrograms/ml, and was lethal to 100% of the cells at concentrations above 1.0 micrograms/ml. TBQ was 6-7 times more cytotoxic to V79 cells than TBHQ, a related BHA metabolite, and 100 times more cytotoxic than BHA. At dose levels of 0.2, 0.4 and 0.6 micrograms/ml of medium, TBQ did not increase significantly the frequency of sister-chromatid exchanges (SCE) in V79 cells and did not consistently increase the frequency of mutation to thioguanine resistance (TGR) at the hgprt gene locus either alone or with activation by rat hepatocytes. Incubation with TBQ for 4 h at pH 3.6 without activation resulted in only small increases in the frequency of gene conversion and reverse mutation in strain D7 of Saccharomyces cerevisiae. However, exposure to TBQ alone in growth medium for 24 h, produced inconsistent results. From these studies it was concluded that TBQ was cytotoxic but not genotoxic to V79 cells; and may be weakly genotoxic to strain D7 of S. cerevisiae.