Skin carcinomas and micronucleus induction in epidermal keratinocytes following 12-O-tetradecanoylphorbol-13-acetate and mezerein treatment.
Phorbol esters are chemical compounds which have the ability to promote carcinogenesis in the skin of mice. In the HRA/Skh mouse strain, an initiation-promotion assay substantiated evidence that mezerein acts as a complete promoter. Complete promotion with 9.0 nmol mezerein induced a total of 53 papillomas in 28 mice within 40 weeks, while 1.5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA), using the same application regime, resulted in a total of 298 papillomas in 58 mice. However, 7.6% of the papillomas in the mezerein group progressed to carcinomas, compared with 0.7% in the TPA group. Approximately the same molar concentrations of TPA and mezerein induced a dose-dependent and reproducible increase in micronuclei in supra-basal cells derived from the epidermis of treated mice. In contrast, the latter compound was less toxic to these cells and induced higher numbers of micronuclei at the higher concentrations.
Steinel
H H
HH
Toxicology Unit, National Institute of Occupational Health and Safety, Camperdown, NSW, Australia.
Bonin
A M
AM
Meher-Homji
K
K
Baker
R S
RS
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004224:Diterpenes; D005260:Female; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D015162:Micronucleus Tests; D012878:Skin Neoplasms / Q000139:chemically induced*; D013729:Terpenes / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D013755:Tetradecanoylphorbol Acetate