Genotoxicity of analgesic compounds assessed by an in vitro micronucleus assay.

Several analgesic compounds and mixtures of analgesics were examined for both cytotoxicity and ability to induce chromosomal damage in the normal rat-kidney cell line NRK-49F. Chromosomal damage was assessed using an in vitro micronucleus assay. Of all the compounds tested, only N-hydroxyparacetamol caused a high degree of cell death at the concentrations used. 4 analgesic compounds were found to be inducers of micronuclei in NRK cells; in order of decreasing potency these were: N-hydroxyparacetamol, N-hydroxyphenacetin, caffeine and paracetamol. An aspirin, phenacetin, caffeine mixture (APC) failed to induce micronuclei above the background level, and a paracetamol-codeine combination did not increase the level of micronuclei induction above that induced by paracetamol alone. This report suggests paracetamol and some related compounds are capable of inducing chromosomal damage in mammalian cells in vitro, which is consistent with recent reports of a possible paracetamol-DNA interaction