TISSUE-SPECIFIC EXPRESSION AND ACTIVATION OF N-METHYLPURINE-DNA GLYCOSYLASE IN THYMIC CARCINOMAS OF TRANSGENIC MICE EXPRESSING THE SV40 LARGE T-ANTIGEN GENE

Simian virus 40 T-tumor antigen (SV40 T-ag) can induce a wide variety of tumors in hamsters and neonatal mice. These tumorigenic effects are predominantly due to the activity of early viral gene products, large T-antigen and small t-antigen. We have analyzed the expression of a D NA repair gene, N-methylpurine-DNA glycosylase (MPG), from different t issues of a non-transgenic (control) and SV40 T-ag expressing transgen ic mice at the mRNA level. Expression of the transgene in thymus of ad ult mice was also detected by the presence of SV40 T-ag mRNA, Non-tran sgenic mice did not express the SV40 T-ag gene in their thymus, while the mRNA for MPG was found in thymus from both of transgenic and nontr ansgenic mice. The MPG gene was expressed in various tissues and is re gulated in a tissue-specific manner. Northern blot analysis revealed t hat the transgenic mice showed considerably higher expression of MPG i n the thymic carcinomas, The level of MPG mRNA in the thymic carcinoma was elevated about 5.7 fold, as compared with those found in the cont rol thymus, MPG expression was significantly increased, either directl y or indirectly, by the SV40 T-ag gene product. These findings provide the first in vivo observations that the SV40 T-ag gene induced thymic carcinomas associated with the activation of the DNA repair gene, MPG .