Quantitative correlation between radiation-induced mutagenesis in endogenous genes and transgenes of mouse spermatogonial stem cells

In order to evaluate the pUR288-plasmid transgenic mouse model, utilizing t he bacteriol lacZ gene as the mutational target, radiation-induced mutagene sis was primarily analyzed in spermatogonial stem cells. A combined hydroxy urea (HU)X-ray treatment protocol was used, known to sensitize dramatically the induction of mutations in endogenous genes. In the testes of untreated animals, a mutant frequency of 6.7 +/- 4.4 x 10(-5) was found. In animals treated with HU or X ray alone, moderate elevations were seen (factors of a bout 4 and 2 over untreated animal values). In testes of mice having receiv ed the HU + X-ray combination treatment, a mutant frequency of 63.0 +/- 36. 1 x 10(-5) was found. The results obtained showed a good quantitative corre lation between endogenous genes and the transgene, indicating the suitabili ty of pUR288 transgenic mice for also efficiently recording radiation-induc ed genetic damage. Radiosensitization, seen in spermatogonial stem cells, w as not observed in other studied organs such as spleen, brain, or lung. (C) 1999 Wiley-Liss, Inc.