Lead acetate does not inhibit dimethylnitrosamine activation and interacts with phenobarbital which is genotoxic in the ST cross of the Drosophila wing spot test

► PH is genotoxic in the ST cross. ► PbAc and PH showed a chemical interaction in the ST cross. ► PH genotoxicity seemed to be inhibited as the PbAc concentration increased, except at the lowest dose. ► PbAc does not inhibit the heme group synthesis since DMN was activated by CYP450s in both crosses. Lead acetate (PbAc) is known to inhibit the synthesis of the heme group, needed for hemeproteins like Cytochromes P450 (CYP450s). Dimethylnitrosamine (DMN) requires metabolic activation by CYP450s. The Drosophila wing spot test was performed to establish whether PbAc inhibits DMN activation in the standard (ST) and high bioactivation (HB) crosses, with different levels of CYP450s. Phenobarbital (PH) was used as an antagonist for its ability to induce CYP450s synthesis. PbAc (0.01, 0.1, 1.0mM) produced significant small spots frequencies in the ST cross, indicating a possible genotoxic activity, however, the total spots frequency was negative at all concentrations. DMN (0.076mM) was genotoxic in both crosses; surprisingly, PH (12mM) was genotoxic and the PH-DMN treatment resulted synergic in the ST cross. Interestingly, the PbAc–PH pre-co-treatments showed a possible interaction in the ST cross. The GC-MS analysis showed a drop in the PH content as the PbAc concentration increased. PbAc also seemed to inhibit the genotoxic activity of PH, except at 0.01mM. It is concluded that PbAc does not inhibit DMN activation by CYP450s in both crosses since it exerted a clear genotoxicity and that PH is genotoxic and interacts with PbAc in the ST but not the HB cross.