Characterization of the induction of ornithine decarboxylase activity by benzoyl peroxide in SENCAR mouse epidermis

The induction of epiderinal ornithine decarboxylase (ODC) activityby benzoyl peroxide (BPO) was characterized to evaluate theusefulness of this effect as a short-term marker of BPO-inducedmouse skin tumor promotion. The maximal induced levels of ODCspecific activity, after a single topical dose of BPO, were>2-fold higher when a cold scraping method was used to prepareepidermis rather than the commonly used heat treatment method.Therefore, the cold scraping method was used for all the workreported here. Application of a single 20 mg dose of BPO tothe dorsal skin of SENCAR mice caused a relatively small inductionof epidermal ODC activity, to a level <1/40 that inducedby a single 2 µg dose of 12-O-tetradecanoylphorbol-13-acetate(TPA). Furthermore, the time-courses of induction were differentafter single doses of TPA and BPO, with peak activities observedat 6 and 24 h after treatment respectively. In contrast, aftera total of five 20 mg doses of BPO were topically applied (onedose every 2 days), ODC activity was transiently induced toan average level >15 times after a single dose. Additionally,on this dosing regimen, the peak of ODC activity shifted to4 h after the last treatment, so that the time-course of ODCinduction resembled that after multiple applications of TPA.The extent of epidermal ODC induction by BPO was found to bea complex function of the frequency of dosing and the numberof treatments. However, when BPO treatments were administeredfrom 1 to 7 days apart, similar maximal induced levels of ODCactivity were eventually achieved after application of multipledoses. Importantly, the dose-response for the induction of ODCactivity by five doses of BPO (applied one dose every 2 days)was highly correlated with published data on the dose-responsefor tumor promotion by this organic peroxide, indicating thatODC induction is a good short-term marker of BPO-induced tumorpromotion in SENCAR mice.