Test-condition-dependent influence of harman and nonharman on benzo[a]pyrene mutagenesis in Salmonella

The enhancing or decreasing effect of harman or norharman on benzo[a]pyrene mutagenesis depends mainly on the metabolizing system (S9) used. When mammalian activation was performed by using liver homogenates from mice induced by 3-methylcholanthrene, phenobarbital or Aroclor 1254, then the mutagenicity of benzo[a]pyrene in Salmonella typhimurium TA98 decreased upon addition of harman or norharman. In the presence of rat-liver homogenate induced by Aroclor 1154, however, harman enhanced the number of benzo[a]pyrene revertants, whereas norharman did not show any significant alteration of the benzo[a]pyrene mutagenicity. Further tests carried out with phenobarbital-induced mouse-liver homogenate showed that, within certain limits, neither variations of the amount of S9 extract nor the amount of the cofactors nor the relative proportions of the test substances had any influence on the antagonistic effect of harman or norharman on the benzo[a]pyrene mutagenesis.