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A study was made of the protective effect of some radioprotective agents against dominant lethal mutations (DLM) in postspermatogonial stages and reciprocal translocations (RT) in spermatogonia induced by gamma-radiation. Among the radioprotective agents used, cystaphos, a combination of cystamine and 5-MOT and a mixture of 6 components proved to be most effective against DLM, and cystaphos, gammaphos and cystamine combined with 5-MOT proved effective against RT. The degree of radioprotective efficacy was relatively low. The efficacy of cystamine in protecting against RT was higher with exposure of gonocytes of 18.5-day embryos than spermatogonia of pubertal animals. The degree of the radioprotective effect varied depending on the stage of spermatogenesis, and, in all cases, it was lower than that observed in studies of protection against lethal effects of ionizing radiation.

The frequency of reciprocal translocations (RT) induced by single injection of tritiated water (THO) (3.3; 6.3 and 12.6 MBq/g) or by referent 137Cs gamma irradiation was studied. The absorbed doses in testis were: 1; 2 and 4 Gr. The frequency of RT per 100 cells were 0.4; 1.1 and 2.5 after THO administration, and 0,5; 0.9 and 1.2 after single exposure to gamma irradiation, respectively. The RBE of tritium increased from 1 at the dose of 1 Gr to 2, at the dose of 4 Gr.

The genetic effect of incorporated radiocarbon was studied after single, long-term (33 days) and chronic (6 and 12 months) treatment of male mice (CBA X C57B1) F1 with [14C]glucose. The genetic effect in male germ cells was estimated by 3 tests: DLM frequency in post- and pre-meiotic cells, RT frequency in stem spermatogonia and frequency of abnormal sperm heads. Absorbed doses in the gonads were: 0.22, 0.50 and 1.01 Gy, after a single exposure; 0.74 and 1.47 Gy, after long-term exposures; and 0.006 and 0.031 Gy, after chronic exposure for 6 months; and 0.013 and 0.066 Gy, for 12 months. The results suggest that DLM frequency in post-meiotic cells increased linearly with increasing the dose of 14C single and long-term exposures at a dose of 1.47 Gy only. A chronic treatment with [14C]glucose induced no increase in DLM frequency. RT frequency in stem spermatogonia was statistically significantly higher than the control level after the single and long-term exposure to 14C. A comparison of the results with the results of external single and chronic gamma-irradiation allows the conclusion that the relative genetic efficiency of radiocarbon as compared with that of gamma-rays is about 1.

Adult male rats were given 1300 rad of chronic gamma-irradiation (0.08 rad/min) Dominant lethal rates were found to be high (ranging from 48 to 75%) in irradiated postmeiotic cells and clearly lower (6.8%) in spermatogonia. The chromosome aberration (reciprocal translocation) yields observed with 1300 rad chronic irradiation were comparatively low, averaging 1.6%. Spermatogonia irradiation at low dose rate resulted in a smaller effect as compared to the genetic effects of a single acute exposure.

Male mice were given mechlorethamine (2.0 mg/kg) followed immediately or 1, 2, 4, or 8 h later by procarbazine (100 mg/kg) and vincristine (0.67 mg/kg) in a protocol that stimulated the drugs and dosages used in a single cycle of clinical MOPP therapy. Seven weeks later and continuing for the next five weeks, the mice were mated to females and the dominant lethal mutant frequencies determined in their offspring by an in vitro assay. Significant (Student's t-test, p less than 0.05) mutant frequencies were detected when the interval between drug administration was between 2 and 8 h. In another series of experiments, mice were injected with these drugs using a 4-h interval between mechlorethamine and the vincristine and procarbazine (MOPP), two cycles of MOPP separated by one week, one cycle of MOPP and 2.0 Gy x-radiation separated by one week, or 2.0 Gy x-radiation alone. When each group was assayed for its dominant lethal mutant frequency, all were found to have similar, highly significant (0.001 less than p less than 0.005) induction. Together these data suggest that stable mutagenic lesions are induced in spermatagonial stem cells by both x-radiation and chemotherapeutic drugs and the frequency with which they are produced can be approximated by a single treatment. Clinical strategies to minimize genetic effects should concentrate on the sequence and timing of drug administration on those days when the drugs are administered in combination.