Detecting genotoxic effects of potential clastogens: An in vivo study using the transgenic lacZ plasmid and the Muta™Mouse model

In the present paper the capacity of the pUR288 plasmid mouse model and the Muta™Mouse model to detect the clastogens bleomycin, m-AMSA, o-AMSA and camptothecin, was investigated. Ethylnitrosourea (ENU) served as a positive control, methylcellulose as a negative control. Only bleomycin induced a slight but significant increase in lacZ mutant frequency (MF) in bone marrow of pUR288 plasmid mice. Exposure to the other compounds did not result in an increase in the MF in bone marrow and liver in both mouse models. For the Muta™Mouse this result was expected, for the plasmid mouse an increase in MF after clastogen exposure was expected. The positive control ENU induced statistically significant increases in MF compared with the negative control in both models and in both tissues analyzed. Hybridisation of DNA of mutant colonies derived from plasmid mice with labelled total mouse DNA (Hybridisation Assay) demonstrated an increase in the percentage of colonies hybridised with total mouse DNA as compared with the negative control, which suggests that there was indeed a biological response associated with treatment. The latter results indicate that the plasmid mouse assay may still be a promising model for the detection of clastogens.