Accumulation of aberrant Y chromosomes in gamma-ray-induced thymic lymphomas lacking p53

Male F-1 hybrids between MSM mice carrying a deficient p53 allele and BALB/ c mice were irradiated with gamma-rays, and 80 thymic lymphomas were obtain ed, 46 of which developed in mice carrying the deficient p53 allele. Becaus e the Y chromosome contributes little to cellular function, the stability o f the Y chromosome in the tumors was assessed by polymerase chain reaction by examining three genes: Smcy and Sry on the short arm and Sts in the pseu doautosomal region of the long arm of the Y chromosome. Twenty-one lymphoma s had lost one or two genes, probably as a result of mitotic recombination or interstitial deletion, whereas no lymphomas had lost all three genes. Th e p53 status of the lymphomas was determined by genotyping and allelic loss analysis, 34 had retained two wild-type p53 alleles, suggesting normal fun ction; 34 had lost both alleles, indicating loss of function; and the other 12 had at least one wild-type p53 allele, so their p53 status was unclear. Compilation of these data revealed that changes in the Y chromosome were d etected in only two of the 34 lymphomas retaining functional p53 but in 18 of the 34 lymphomas lacking p53 function, suggesting that p53 deficiency le ads to an increase in the accumulation of radiation-induced aberrant chromo somes. This is consistent with our previous result from analysis of the ina ctive X chromosome. In contrast, a decrease in the fidelity of mitotic tran smission in p53-deficient lymphomas was not noted for the Y chromosome. (C) 1999 Wiley-Liss, Inc.