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Mutagenicity of γ‐radiation, mitomycin C, and etoposide in the Hprt and Tk genes of Tk +/− mice †
Author(s) -
Dobrovolsky Vasily N.,
Shaddock Joseph G.,
Heflich Robert H.
Publication year - 2002
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.10074
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , microbiology and biotechnology , biology , mitomycin c , mutant , gene , dna damage , dna repair , somatic cell , dna , gene mutation , mutation , genetics
The recently developed Tk +/− mouse detects in vivo somatic cell mutation in the endogenous, autosomal Tk gene. To evaluate the sensitivity of this model, we have treated Tk +/− mice with three agents that induce DNA damage by different mechanisms, and determined spleen lymphocyte mutant frequencies (MFs) in the autosomal Tk gene and in the X‐linked Hprt gene. γ‐Radiation, which produces single‐ and double‐strand breaks by nonspecific oxidative stress, efficiently increased Hprt MF, but not Tk MF. Mitomycin C, which produces bulky DNA monoadducts and crosslinks, was mutagenic in both the Hprt and Tk genes, but the response was greater in the Tk gene. An inhibitor of the ligase function of DNA topoisomerase II, etoposide, did not increase Hprt MF, and induced a small, but nonsignificant increase in Tk MF. Combined with previous data, the results indicate that the two genes are differentially sensitive to many agents, and that the Tk gene is more sensitive than the Hprt gene to some, but not all types of DNA damage. Environ. Mol. Mutagen. 39:342–347, 2002. Published 2002 Wiley‐Liss, Inc.