The "promoting" activity of methyl methanesulphonate in rat bladder carcinogenesis

The carcinogenic activity of the alkylating agent methyl methanesulphonate (MMS) was investigated in the F344 rat bladder, both untreated and pretreated with a single threshold dose of N-methyl-N-nitrosourea (MNU). On its own, 6 doses of 2.5 mg MMS produced a 7% incidence of bladder cancer. After a single intravesical instillation of MNU, the same MMS treatment produced a bladder cancer incidence of 56%. This was significantly higher than the incidence (24%) observed after treatment with MNU alone, and greater than the sum of the lesions produced by either treatment alone. By reference to the mouse skin multistage carcinogenesis model, it is argued that MMS is a complete, albeit weak carcinogen with little initiating but powerful late-stage activity. Its promoting activity is most probably attributable to its potent mitogenic action and in this model it is analogous to a stage 2, rather than a stage 1 skin promoter.