Biological assays for irritant tumor-initiating and -promoting activities. I. Kinetics of the irritant response in relation to the initiation-promoting activity of polyfunctional diterpenes representing tigliane and some daphnane types.

The kinetics of the irritant response on the mouse ear [erythema measured quantitatively by the irritant dose 50 (ID50)] and its relation to the initiation-promoting activity on the back skin of NMRI mice of some polyfunctional diterpene esters were investigated: (1) A very rapid and transient erythema response is associated with low or absent promoting activity (2) an early and more persistent erythema response in most cases is associated with moderate-to-high promoting activity, and (3) a relatively late onset but persistence up to at least 24 h of the erythema response is associated with high promoting activity. These results may indicate a relationship between the kinetics of the erythema response and the initiation-promoting activity of diterpene esters. The comparatively low promoting activity of esters carrying polyunsaturated acyl functions may indicate the importance of pharmacological parameters such as bioavailability and stability in the biological system, drug-receptor interaction, and "intrinsic activity" of the diterpene esters.