Ornithine decarboxylase activity in chemically induced mouse skin papillomas

The activity levels of L-ornithine carboxy-lyase (ODC) (E.C.4.1.1.17[EC]) and S-adenosyl-L-methionine carboxy-lyase (SAMD) (E.C.4.1.1.50[EC]) were determined in individual papillomas induced inmouse skin by a two-stage technique, and in normal mouse epidermis.Cycloheximide treatment abolished both enzyme activities. Innormal epidermis the ODC activity was barely detectable, whereasthe tumors exhibited high levels of ODC. Levels of SAM-D activityabove those of normal epidermis were detected in some papillomas,but in contrast to ODC the SAM-D activity levels were not consistentlyincreased in skin tumors. By pooling a great number of papillomas,the variations in ODC and SAM-D activities between differentpapillomas could be minimized so that reliable measurementsof the biological half-lives of ODC and SAM-D in the tumorswere obtained using cycloheximide treatment. The half-life ofSAM-D in squamous papillomas was 45 min, almost identical tothe 41 min half-life of the 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced level of this enzyme in normal mouse epidermis.In contrast, the ODC activity of the mouse skin papillomas declinedat a rate similar to that in TPA-treated epidermis for onlythe first 15–20 min after cycloheximide injection. Thereafter,at time points when protein synthesis was 90% inhibited, theODC activity reverted to high levels. These results show thatthe high level of ODC activity in squamous papillomas is stabilized.This observation is compatible with the hypothesis that thecontrol mechanism of the ODC activity level in these tumorsis severely deranged. This change in polyamine turnover patternmay be related to altered differentiation of the epidermal cells,which constitute the main bulk of cells in these tumors.