Sequencing analysis of Ha‐, Ki‐, and N‐ras genes in rat urinary bladder tumors induced by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) and sodium saccharin

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Abstract
Male F344 rats were fed N[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) for up to 4 wk, then given the basal diet with or without 5% sodium saccharin for up to 100 wk. In a previous study, we demonstrated point mutations in codons 12 and 61 of Ha‐ras gene among eleven transitional cell carcinomas (TCC), one undifferentiated carcinoma, and two sarcomas of the urinary bladder (Mol Carcinogen 3:210–215, 1990). In this study, Ha‐ras, Ki‐ras, and N‐ras sequences were examined by polymerase chain reaction (PCR) and direct DNA sequencing. The results confirm the point mutation in codon 61 (CAA to CGA in 5 TCCs and to CTA in one TCC) of the Ha‐ras gene. Mutation at codon 12 was not confirmed. No mutation was found in the Ki‐ras gene. Sequences of the N‐ras gene exons 1 and 2 were determined, and no mutations was detected. These results suggest the involvement of activated Ha‐ras gene, but not Ki‐N or N‐ras gene, in rat urinary bladder carcinogenesis induced by FANFT. Subsequent sodium saccharin administration did not affect the changes in Ha‐ras gene. ©1993 Wiley‐Liss, Inc.