TY - JOUR
T1 - Induction of dark keratinocytes by 12-o-tetradecanoyl-phorbol-13-acetate and mezerein as an indicator of tumor-promoting efficiency
AU - Klein-szanto, Andres J.P.
AU - Major, Suzanne K.
AU - Slaga, Thomas J.
PY - 1980/5/1
Y1 - 1980/5/1
N2 - 12-O-Tetradecanoylphorbol-13-acetate (TPA) and mezerein (MZ) are diterpene esters of similar structure and approximately equipotent on a molar basis as far as their hyperplaslogenic, inflammatogenic, and induction of ornithine decarboxylase activity effects in mouse skin are concerned. On the other hand, TPA is much more effective than MZ as a tumor promoter. The percentage of dark basal keratinocytes was determined in the interfollicular epidermis (IFE) of mice topically treated with 1, 2, or 4 μg of either TPA or MZ in a single application and studied at 12, 24, 48, 96, and 144 h thereafter. The results showed that TPA induced 2 to 3 times more dark cells than MZ in the IFE as well as in the infundibular portion of the hair follicle. The latter epithelium presented a larger number of dark keratinocytes than the IFE in all experimental and control situations, and the differences between the effects of TPA and MZ were even greater in the infundibular epidermis than in the IFE. TPA induced an increase of 5 to 11 times over the control number of dark cells (̃2% IFE), reaching maximum values of 21% in the basal layer 24 h after topical application of 4 μg of TPA. MZ only produced a 3- to 6-fold increment. The labeling indices of the basal layer and of the dark basal cells were markedly and similarly increased with both compounds. The different dark-cell inducing characteristics seem to be the only detectable difference in early effects produced by TPA and MZ and would point to the importance of the production of the dedifferentiated dark cells during early stages of tumor promotion.
AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) and mezerein (MZ) are diterpene esters of similar structure and approximately equipotent on a molar basis as far as their hyperplaslogenic, inflammatogenic, and induction of ornithine decarboxylase activity effects in mouse skin are concerned. On the other hand, TPA is much more effective than MZ as a tumor promoter. The percentage of dark basal keratinocytes was determined in the interfollicular epidermis (IFE) of mice topically treated with 1, 2, or 4 μg of either TPA or MZ in a single application and studied at 12, 24, 48, 96, and 144 h thereafter. The results showed that TPA induced 2 to 3 times more dark cells than MZ in the IFE as well as in the infundibular portion of the hair follicle. The latter epithelium presented a larger number of dark keratinocytes than the IFE in all experimental and control situations, and the differences between the effects of TPA and MZ were even greater in the infundibular epidermis than in the IFE. TPA induced an increase of 5 to 11 times over the control number of dark cells (̃2% IFE), reaching maximum values of 21% in the basal layer 24 h after topical application of 4 μg of TPA. MZ only produced a 3- to 6-fold increment. The labeling indices of the basal layer and of the dark basal cells were markedly and similarly increased with both compounds. The different dark-cell inducing characteristics seem to be the only detectable difference in early effects produced by TPA and MZ and would point to the importance of the production of the dedifferentiated dark cells during early stages of tumor promotion.
UR - http://www.scopus.com/inward/record.url?scp=0019301949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0019301949&partnerID=8YFLogxK
U2 - 10.1093/carcin/1.5.399
DO - 10.1093/carcin/1.5.399
M3 - Article
C2 - 6168406
AN - SCOPUS:0019301949
VL - 1
SP - 399
EP - 406
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 5
ER -