Base Substitution Mutations Induced by the Mycotoxin Citrinin

Abstract

The mycotoxin citrinin, a secondary metabolite of toxigenic strains of Penicillium citrinum and more than 20 other Penicillium and Aspergillus species, belongs to the natural, environmental toxins. Contaminations, especially of grains but also of other food and feedstuffs, have been reported. Citrinin is considered as a nephrotoxin. Reports on the mutagenicity of citrinin are controversial. Shinohara et al. (1976) and Kanisawa (1984) found a cocancerogenic effect of citrinin in combination with other substances in rats and mice. In short-term mutagenicity tests like the Ames and the SOS chromotest, several groups of investigators, including the present authors, have obtained negative results, whereas in the Rec and PolA test results have been positive (Kuczuk et al. 1978; Ueno et al. 1978; Ueno and Kubota 1976; Wehner et al. 1978). Recently, it has been shown that citrinin causes single- and double-strand breaks in the DNA of intact E. coli cells and induces DNA repair synthesis in permeabilized E. coli cells (Martin et al. 1986). In vitro the mycotoxin produces celavage of ColE1 plasmid and lamda DNA in the presence of small amounts of copper ions. It was proposed that citrinin generates in combination with metal ions hydroxyl radicals and also radicals of the quinone moiety of citrinin, which are responsible for the DNA-destroying activity of the mycotoxin (Martin et al. 1986). In order to investigate whether such DNA damage leads to mutagenesis, we employed the E. coli-phage M13am6H1 system of Brandenburger et al. (1981).

This paper is presented in tribute to the memory of Prof. R. J. Röschenthaler