TISSUE-SPECIFIC EXPRESSION OF THE K-RAS ALLELE FROM THE A J PARENT IN(A/J X TSG-P53) F1-MICE/

Tissue-specific expression of parental K-ras allele(s) was investigate d by single-strand conformation polymorphism analysis of the 3' untran slated region of the K-ras gene in normal lung, spleen, liver and kidn ey from (A/J x TSG-p53) F-1 mice. The expression of A/J K-ras allele w as equal to that of C57BL/6J allele in normal spleen, liver and kidney . However, transcripts from A/J K-ras allele were found to be 2-12-tim es greater than those from C57BL/6J allele in lung tissues harvested o ver a 20-week period. Similar to our previous observation with dimethy lnitrosamine- and benzo[a]pyrene-induced lung tumors, K-ras mRNA trans cribed from A/J allele was 10-40-times more abundant than those from C 57BL/6J allele in all of 40 (A/J x TSG-p53) F-1 mouse lung tumors indu ced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. In addition, K- ras mutations (G to A transitions at the second base of codon 12) were detected in 38 of 40 (95%) lung tumors and all of the mutations were found on the allele inherited from the A/J parent. These data demonstr ate tissue-specific allele-specific transcription of the K-ras gene an d provide further support to the thesis that K-ras allele itself is a primary mouse lung tumor susceptibility gene.