Moderate enhancement of the promotion phase of skin tumorigenesis in hairless mice by topical pretreatment with a mitosis-inhibiting epidermal pentapeptide.
The effect of the physiological epidermal proliferation inhibitory substance (EPP) pGlu-Glu-Asp-Ser-GlyOH on the promotion phase in two-stage carcinogenesis was investigated. EPP could be the active component in what has been called epidermal chalone. Hairless mice were given an initial application of 100 nmol 7,12-dimethylbenz[a]anthracene in 200 microliters acetone. One week later promotion was started with topical applications of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week. Ninety minutes before each TPA application the control group received a topical application of 200 microliters reagent grade acetone and the two experimental groups were given either 0.005% or 0.01% EPP in 200 microliters acetone. The mice were observed for time of occurrence and time of regression of papillomas. The number of tumors produced by the group given the inhibitory substances before TPA increased, and so did the percentage of tumor-bearing animals. There was also a tendency towards a higher degree of papilloma regression in the animals treated with EPP before TPA. We have previously shown that EPP enhances methylnitrosourea (MNU) carcinogenesis. Since we regard TPA as a skin-irritating promoter with weak carcinogenic potency, very different from MNU, the fact that EPP has the same enhancing effect on promotion as it has on complete MNU carcinogenesis raises some very interesting questions, and may indicate a similarity between the mechanisms in promotion and complete carcinogenesis. Some possible explanations of the results are discussed, e.g. whether the transit zone late G1/S of the cell cycle is the most sensitive one for carcinogenic or tumorigenic effects.
Iversen
O H
OH
Institute of Pathology, University of Oslo, Norway.
Elgjo
K
K
Paulsen
J E
JE
Reichelt
K L
KL
D015127:9,10-Dimethyl-1,2-benzanthracene; D000287:Administration, Topical; D000595:Amino Acid Sequence; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000633:toxicity*; D010212:Papilloma / Q000139:chemically induced*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate
D002273:Carcinogens; D009842:Oligopeptides; C050550:epidermal pentapeptide; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate; D011761:Pyrrolidonecarboxylic Acid