title: Quantitative correlation between radiation-induced mutagenesis in endogenous genes and transgenes of mouse spermatogonial stem cells.
abstract: 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.
authors.affiliation: Novartis Pharma AG, Preclinical Safety: Toxicology/Pathology, Basel, Switzerland. hansjoerg.martus@pharma.novartis.com
authors.forename: H J
authors.initials: HJ
authors.lastname: Martus
authors.forename: M
authors.initials: M
authors.lastname: Novak
authors.forename: D
authors.initials: D
authors.lastname: Blecher
authors.forename: A
authors.initials: A
authors.lastname: van Duyn-Goedhart
authors.forename: W
authors.initials: W
authors.lastname: Suter
authors.forename: J A
authors.initials: JA
authors.lastname: Gossen
authors.forename: P P
authors.initials: PP
authors.lastname: van Buul
mesh_terms: 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
chemical_list: D006918:Hydroxyurea