ALTERED PROTEIN EXPRESSION DETECTED IN THE F1 OFFSPRING OF MALE-MICE EXPOSED TO FISSION NEUTRONS

Liver protein expression in F-1 offspring arising from spermatogonia e xposed to 60 cGy of fission spectrum neutrons from the JANUS reactor w as compared to that in offspring from unexposed spermatogonia by using two-dimensional electrophoresis (2DE). Approximately 100 protein spot s in 2DE patterns from 167 control offspring and 530 offspring from ir radiated sires were monitored for quantitative decreases of 50%, indic ative of mutation events causing the loss of one normal copy of a stru ctural gene. Reproducible abnormalities were found only in 3 patterns, all from the offspring of neutron-irradiated sires. Two of the three patterns were from littermates (brother and sister) and both showed an approximately 70% decrease in the amount of liver protein MSN188. The third pattern was from a male mouse sired by a different male and sho wed an approximately 50% decrease in the abundance of protein MSN94. T he decreased abundance of MSN188 and MSN94 was assumed to be due to mu tation events referred to as NEUT1 and NEUT2, respectively. Sibling cr osses between the 2 mice showing the NEUT1 trait produced offspring wi th control, decreased and undetectable levels of MSN188 in a ratio of 0.25:0.5:0.25. Test crosses between the F-1 offspring expressing the N EUT2 trait back to C57BL/6JANL mice produced offspring expressing norm al or decreased amounts of MSN94 in a ratio of 0.5:0.5. Inbreeding of individuals expressing decreased amounts of MSN94 produced mice expres sing control, decreased amounts, or no detectable amount of that prote in in a ratio of 0.25:0.5:0.25. These results indicate that the decrea sed abundance of MSN188 or MSN94 originally detected in the F-1 offspr ing is due to a genetically transmissible event. Unlike the heritable protein changes observed previously in the F-1 offspring of sires expo sed to N-ethyl-N-nitrosourea in which a protein variant was produced, both the NEUT1 and NEUT2 mutation events appear to prevent the product ion of any protein product. These 2 mutations may thus represent mutat ion lesions other than point mutations (e.g., deletions or translocati ons) detectable as quantitative changes in protein expression in the F -1 generation.