RESUMO
The synthesis of histone mRNA is closely coupled with DNA replication. During the S-phase of the cell cycle, the level of histone mRNA increases over fifty fold then rapidly disappears at the start of G2-phase. The presence, therefore, of abundant quantities of histone mRNA provides a molecular marker of cycling cells. The expression of histone mRNA was investigated by in situ hybridization method in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced rat bladder tumor to determine the proliferation patterns. This method resulted in intense brown/black cytoplasmic staining of cells containing histone mRNA and extent and intensity of stain were increased in tumorigenesis (normal, simple hyperplasia, nodular or papillary hyperplasia, and transitional cell carcinoma-Ta,T1). The higher S-phase fraction indicated greater biological malignancy based on the fact that the extent and intensity of stain progressively increased with tumorigenesis.