Comparative mutagenicity testing of bropirimine, 1. Induction of chromosome aberrations in CHO cells is not reflected in induction of mutation at the TK locus of L5178Y cells

Abstract

Bropirimine (U-54,461) is a novel compound which is being developed as a biological response modifier for use in treatment of neoplastic and viral disease. Compounds of this type exert their therapeutic effects by immuno-stimulation or other non-cytotoxic mechanisms. The purpose of the experiments described in this paper was to evaluate the hazard potential of this drug. Bropirimine was previously reported to be negative in the Ames Salmonella assay (Aaron et al., 1989a) and the in vitro UDS assay (Aaron et al., 1989b). In experiments reported here positive response was observed in a test for clastogenicity in vitro in CHO cells, but bropirimine was negative in the L5178Y mouse lymphoma TK +/− assay. A subsequent experiment demonstrated the ability of bropirimine to induce HPRT mutations in CHO cells. Interestingly, evidence for induction of chromosome aberrations in the L5178Y cells by bropirimine was also obtained. While the reason for the apparent insensitivity of the L5178Y TK +/− assay to bropirimine is unexplained by the experiments, it is clear that at high dose bropirimine is capable of clastogenesis in both CHO and L5178Y cells and can give rise to gene mutations in CHO cells but apparently not in L5178Y cells.