Frequency of active ras oncogenes in human bladder cancers associated with schistosomiasis.

The frequency of active ras oncogenes in human bladder cancers associated with schistosomiasis, the cause of which is suspected to be a chemical carcinogen(s) in urine, was examined. Of 9 squamous cell carcinomas of the bladder surgically obtained in Egypt, none scored as positive in the regular DNA transfection assay using NIH/3T3 cells as recipients. The restriction fragment length polymorphism assay at codon 12 of the H-ras gene confirmed the absence of an activating mutation at this site in all of them. Western blotting analysis of electrophoretic mobilities of the ras p21 proteins, a method which can detect at least some of the point mutations within codons 12 and 61 of ras genes, suggested a point mutation within codon 61 in one out of the 7 tumors analyzed. In contrast to the low frequency of detection of mutationally activated ras oncogenes, enhanced expression of the ras p21 proteins was demonstrated in 4 of them by this analysis. The carcinogenic process involved in the endemic bilharzial bladder cancers is thus not associated with detectable point mutations within ras genes at a higher frequency than those in non-bilharzial bladder cancers in Japan or the USA.