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 the bacterial lacZ gene as the mutational target, radiation-induced mutagenesis was primarily analyzed in spermatogonial stem cells. A combined hydroxyurea (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 about 4 and 2 over untreated animal values). In testes of mice having received 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 correlation between endogenous genes and the transgene, indicating the suitability of pUR288 transgenic mice for also efficiently recording radiation-induced genetic damage. Radiosensitization, seen in spermatogonial stem cells, was not observed in other studied organs such as spleen, brain, or lung.
Martus
H J
HJ
Novartis Pharma AG, Preclinical Safety: Toxicology/Pathology, Basel, Switzerland. hansjoerg.martus@pharma.novartis.com
Novak
M
M
Blecher
D
D
van Duyn-Goedhart
A
A
Suter
W
W
Gossen
J A
JA
van Buul
P P
PP
D000818:Animals; D006918:Hydroxyurea / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D010957:Plasmids; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects*; D019076:Transgenes
D006918:Hydroxyurea