Genetic control of differential effects of ethylene oxide in mice

Mouse strains SEC/R1, BALB/c, and SWR/J do not survive more than 20 exposures to ethylene oxide (EtO) at 250 ppm six hours per day, five days per week. Strain C57BL/6 survives beyond 50 exposures when similarly exposed. EtO sensitivity is due to the presence of a single pair of recessive genes by evidence from several backcross populations and the CXB/By recombinant inbred set. Linkage analyses were done and although the exact location of this gene was not found, roughly 50% of the mouse genome was excluded from linkage. EtO has a differential effect on somatic cells. Hemorrhaging and proximal tubule necrosis of the kidney were observed only in sensitive strains. Calcium oxalate crystals were seen in kidneys of SEC but not C57BL/6. The possible metabolic pathway for EtO through ethylene glycol to oxalic acid by alcohol and aldehyde dehydrogenases was investigated. EtO has a differential effect on germ cells. Histological sections and dominant lethal tests have shown that the germ cells of SEC are more susceptible to EtO-induced damage than the germ cells of C57BL/6. The spermatocyte is the stage most susceptible to damage in SEC; the spermatid in C57BL/6.