ENHANCEMENT OF MYELOTOXICITY INDUCED BY REPEATED IRRADIATION IN MICE EXPOSED TO A MIXTURE OF GROUNDWATER CONTAMINANTS

As part of a program on the toxicology of chemical mixtures at the Nat ional Institute of Environmental Health Sciences/National Toxicology P rogram (NIEHS/NTP), hematopoietic functions were studied in female B6C 3F1 mice treated with 0, 1%, and 5% of a chemical mixture stock of 25 groundwater contaminants in drinking water for 31.5 weeks. The toxicol ogic interaction between continuous exposure to groundwater contaminan ts and stress induced by multiple irradiation on hematopoiesis was inv estigated. For those mice receiving both the chemical mixture and irra diation, the exposure to the former was continuous throughout the 31.5 -week experimental period, whereas whole body irradiations (4 times at 200 rads/each) were carried out at 7-week intervals with the first on e at 3.5 weeks. Myelotoxicity assessment was made by determining the n umber of granulocyte-macrophage progenitor cells (CFU-GM) 1 week after each irradiation and also at 6 weeks following irradiation as a measu re of recovery from stress. Non-irradiated mice treated with 5% chemic al mixture solution showed suppression of CFU-GM after 15.5 weeks and became progressively more affected (only 70% of controls by 31.5 weeks of treatment). The population of CFU-GM in mice treated with 5% chemi cal mixture for 4.5 weeks plus irradiation (I week after first irradia tion) was only 22% of the non-irradiated vehicle control group. This c ombined (i. e., chemical mixture plus irradiation) suppression of CFU- GM intensified after repeated irradiation until the number of CFU-GM w as only 10.7% following the fourth irradiation at 25.5 weeks. Thus, ir radiation caused a significant reduction in CFU-GMs in all mice but th e effects were more pronounced in mice treated with a chemical mixture . In the chemical mixture pretreated mice, the hematopoietic cells wer e depressed more by multiple irradiation, and the recovery was delayed as compared to non-irradiated control. Furthermore, even at 1% mixtur e stock level (the lowest concentration tested), when all routine hema tologic or conventional toxicologic endpoints appeared to be normal, a n enhancement of radiation injury to hematopoiesis was detected. It is suggested that a residual. subclinical, bone marrow effect of the che mical Mixture renders the mice more sensitive to subsequent irradiatio n-induced injury and also prolongs the recovery of mice following mult iple irradiation. These findings suggest that long-term exposure to hi ghly contaminated driking water may render a population more susceptib le to subsequent hematopoietic stress.