Effect of Thiram on Cytochrome P-450 Studied by the Cypia-Test

Abstract

The double CPIA-test (cytochrome P-450 induction assay) as described by Lesca et al. (7) was used to discriminate between the forms of cytochrome P-450 [the phenobarbital (PB)-3-methylcholanthrene (3-MC)-type) induced by thiram, a dithiocarbamate fungicide. The test consisted of studies by the technique of Ames for the ability of the S-9 preparation obtained from livers of rats induced by thiram to cause metabolic activation of ethidium bromide (EtBr) (for 3-MC type) or cyclophosphamide (CPA) (for PB-type of cytochrome P-450). The mutagenicity of activated EtBr or CPA was checked with TA 98 and TA 100 strains of S. typhimurium respectively.

It was found that thiram at 100mg/kg of body weight, while only slightly increasing the 3-MC-type of cytochrome P-450 (400 his ⁺ revertants/ug of EtBr as compared to 2200 his ⁺ revertants/ug of EtBr for 80mg of 3-MC/kg of body weight) caused a noticeable induction of the PB-type (800 his ⁺ revertants/ 800 ug of CPA as compared to 1300 his ⁺ revertants/800 ug of CPA for 50mg of PB/kg of body weight). The direct measurements performed on livers of rats induced with thiram showed no overall changes in the level of cytochrome P-450 but a shift in absorption maximum to 449 nm.