Photomutagenicity of thiabendazole, a postharvest fungicide, in bacterial assays

Abstract

We investigated the photomutagenicity of thiabendazole (TBZ), a postharvest fungicide commonly used on imported citrus fruits. Using UVA light (320-400 nm), we irradiated bacterial cultures with or without TBZ in a 24-well multiplate. UVA-irradiation without TBZ was not mutagenic to the tester strains, nor was unirradiated TBZ. TBZ was strongly photomutagenic in Escherichia coli WP2uvrA and WP2uvrA/pKM101 strains, weakly photomutagenic in Salmonella typhimurium TA100 and TA98, and not photomutagenic in S. typhimurium TA1535 and TA1538. The photomutagenicity of TBZ was more evident in WP2uvrA/pKM101, which carries the trpE65 ochre mutation (TAA), than in TA100, which carries the hisG46 missense mutation (CCC). In E. coli WP3101-WP3106 and the corresponding pKM101-containing strains, photoactivated TBZ induced predominantly G:C-->A:T transitions and A:T-->T:A transversions. In the plasmid-containing strains only, TBZ induced a moderate number of A:T-->G:C transitions and a few A:T-->C:G and G:C-->T:A transversions. The observation that UVA-irradiated TBZ mutated both G:C and A:T basepairs may explain why WP2uvrA/pKM101 was more sensitive to its mutagenicity than TA100. TBZ that was irradiated before it was added to the WP2uvrA/pKM101 cells was not photomutagenic, which suggests that the photomutagenic products of TBZ were unstable or rapidly reacted with other molecules before being incorporated into cells.

Genotoxicidad de tres plaguicidas utilizados en la actividad bananera de Costa Rica

“…Lo anterior concuerda con otras investigaciones que tampoco a y b: Diferencias significativas con el control negativo correspondiente p< 0.0001 con la prueba t-student. observaron efecto genotóxico del tiabendazol en ensayos in vivo e in vitro de aberraciones cromosómicas y con los estudios de mutagenicidad y carcinogénesis en ratones, conejos y bacterias (Lankas et al 2001, Tada et al 2001, Watanabe-Akanuma et al 2003. Además, el tiabendazol presenta una débil actividad aneugénica en células somáticas y germinales que es característica de los compuestos químicos relacionados al benzimidazol (Mailhes et al 1997).…”

“…Además, el tiabendazol presenta una débil actividad aneugénica en células somáticas y germinales que es característica de los compuestos químicos relacionados al benzimidazol (Mailhes et al 1997). Watanabe-Akanuma et al (2003) no observaron efectos mutagénicos en bacterias expuestas a tiabendazol. Sin embargo, informaron sobre su capacidad mutagénica cuando es fotoactivado con luz UV.…”

Analysis of Photomutagenicity of Thiabendazole with UVA Irradiation: Absence of 8-Hydroxyguanosine Formation

“…We previously reported that TBZ shows potent photomutagenicity following UVA irradiation (320-400 nm) for 10 min at a dose rate of 2.5 J/m 2 /sec in Escherichia coli strain WP2uvrA/pKM101 and S. typhimurium strains TA97, TA104, and TA100 (1)(2)(3). Structurally related compounds containing imidazole or thiazole, such as benomyl, mefenacet, tricyclazole, and imazalil are widely used in agriculture as pesticides.…”

“…TBZ photomutagenicity is observed when bacterial cells are irradiated with UVA in its presence, but neither pre-irradiation of TBZ just before adding the cells, nor pre-treatment of cells with TBZ before UVA-irradiation generates mutagenicity (1,3). It seems likely, therefore, that the photomutagenic TBZ products are unstable and/or rapidly react with other molecules before being incorporated into the cells.…”

Inhibitory effects of NADH/NADPH in S9 mix on photo-mutagenicity of thiabendazole following UVA-irradiation in E. coli

“…Although TBZ is reported to be cytotoxic to the spindle apparatus and mitosis in mammalian cells (Styles and Garner, 1974;Mudry de Pargament et al, 1987;Parry and Sors, 1993), it is not mutagenic in bacterial reverse mutation tests with or without metabolic activation (Cancer Assessment Document, EPA, 2000). We recently reported that TBZ shows potent mutagenicity following UVA-irradiation (320 400 nm) for 10 min at 250 µW/cm 2 and that Trp + reverse mutations in Escherichia coli WP2uvrA/pKM101 strain is more sensitive than His + reverse mutations in Salmonella typhimurium strains TA100 and TA98 (Watanabe-Akanuma et al, 2003). The predominant mutations induced by UVA-activated TBZ were G:C A:T transitions and A:T T:A transversions.…”