Effects of formalin-induced injuries on urinary bladder carcinogenesis.

In multistage carcinogenesis, promotion is a long-term or repeated growth stimulation of initiated cells. Possible effects of regenerative hyperplasia induced by repeated intravesical instillation of 0.3% formalin solution on urinary bladder carcinogenesis were examined using heterotopically transplanted rat urinary bladders (HTBs) initiated by N-methyl-N-nitrosourea. The HTB system was chosen because in this system, transient generalized hyperplasia lasting less than a week can be induced readily and repeatedly by intravesical instillation of the formalin solution. No statistically significant tumor enhancement was observed after 15 formalin treatments administered in 30 weeks. It appears that regenerative cytotoxic stimuli, even multiple, may have no significant tumor-promoting activity. Discussed is the possibility that mild and, more importantly, persistent non-cytotoxic stimuli may be more effective as tumor promoters.