Residual hematopoietic effect in mice exposed to ochratoxin A prior to irradiation

Ochratoxin A (OCT A) has the potential to cause myelotoxicity in addition to the well-known toxic effects on the liver and kidney. Whereas in previous studies the bone marrow parameters were examined shortly after injection, experiments reported here were designed to determine whether mice would recover from the myelotoxic effects induced to OCT A injection and secondly whether mice previously injected to OCT A would be more sensitive to radiation-induced myelotoxicity than vehicle controls. Six-week old female B6C3F1 mice were injected intraperitoneally on alternate days over a week with a total dose of 20 or 40 mg/kg of OCT A and bone marrow parameters monitored for up to 16 weeks. Controls received vehicle alone. There was a suppression of marrow granulocyte macrophage progenitors (CFU-C) in OCT A-treated animals which returned to normal values by 2 weeks (20 mg/kg group) or by 5 weeks (40 mg/kg group) following the last treatment. Some of the OCT A-treated mice were additionally irradiated with 200 rads of whole body irradiation (WBI) at 10 and 52 days following OCT A injections. Irradiation caused a significant reduction in CFU-Cs in all mice but the effects were more pronounced in the mice that had received OCT A previously. The bone marrow parameters of 40 mg/kg OCT A-treated mice returned to normal by 6 weeks after first WBI. A second WBI produced similar depression in CFU-Cs with again a delayed 8 weeks recovery as compared to controls in both dose groups of OCT A-treated mice. The delayed recovery in bone marrow progenitors was also reflected in lower peripheral white blood counts after the second irradiation in 40 mg/kg OCT A-treated mice as compared to the untreated irradiated controls. This indicated that residual bone marrow effect of OCT A makes the mice more sensitive to subsequent irradiation induced injury.