title: Mutagenesis in vivo in T cells of p21-deficient mice.
abstract: Mice that are deficient in p53 exhibit an early onset of multiple types of tumors, especially thymic lymphoma. However, it remains unclear to what extent each of the p53-regulated pathways exerts its tumor suppressor activity. p21(Cip1/Waf1), acting down stream of p53, is a major G1/S checkpoint protein that restricts cell cycle progression into S phase in the presence of DNA damage. While at old ages p21-/- mice have a higher incidence of many types of tumors than p21+/+ mice, they are more resistant to thymic lymphomagenesis. In this study, we characterized mutagenesis in vivo in T cells of p21-deficient mice, using loss of heterozygosity (LOH) at Aprt locus as an indicator. We found that the spontaneous Aprt mutant frequency in T cells of p21-/- mice is lower than that in p21+/+ mice. The mutational spectra, however, are similar, with mitotic recombination being the predominant pathway. In contrast to the remarkable induction of LOH events in T cells of p53-/- mice exposed to X-rays, LOH in T cells of p21-/- mice is not significantly induced by X-rays. Correspondingly, lymphoid cells of p21-/- mice are more sensitive to IR-induced apoptosis than those of p21+/+ mice, in contrast to the radioresistance of p53-deficient lymphocytes. Reduction in mutation load in T cell lineages may contribute to the suppression of thymic lymphomagenesis in p21-/- mice.
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA. shao@biology.rutgers.edu
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Yanping
authors.initials: Y
authors.lastname: Chen
authors.forename: Betty
authors.initials: B
authors.lastname: Zheng
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.forename: Minjie
authors.initials: M
authors.lastname: Luo
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis; D013601:T-Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000228:Adenine Phosphoribosyltransferase