Effects of some pyrrolic and dihydropyrrolizine esters on mouse skin: a preliminary study

Groups of male BALB/c mice were given 33 to 35 treatments during 52 to 54 weeks with 5 ester alkylating agents. Two of these (I and II) were potential metabolites of carcinogenic pyrrolizidine alkaloids; the others (III-V) were chemically similar synthetic compounds. Each dose of 0.5 or 1.0 mumol, in acetone, was applied to the shaved dorsal skin. A control group received acetone. Three skin tumours and 2 preneoplastic lesions were found among 9 mice receiving the compound IV, the agent giving the slowest chemical alkylation reactions. No skin tumours were seen in the other groups. The results suggest that the relationship between carcinogenic potential and alkylating reactivity in this series of compounds should be further investigated.