Malignant conversion of UV radiation and chemically induced mouse skin benign tumors by free-radical-generating compounds.
It is known that the free-radical-generating compound, benzoyl peroxide (BPO) enhances malignant conversion of murine skin benign papillomas into carcinomas. To further define the role of free radicals in malignant conversion, we studied the effect of various free-radical-generating compounds on the conversion of benign papillomas into carcinomas in murine skin. Papillomas were induced in Sencar mice by 7,12-dimethylbenz[a]anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion and in SKH-1 hairless mice by biweekly exposure to UVB radiation. After 20 and 27 weeks respectively, papilloma yield stabilized and no new tumors developed. Skin application of acetone, TPA, BPO, 2,2-azobis(2-amidino-propane) (ABP) and tert-butyl hydroperoxybenzoic acid (BPB) increased the rate of malignant conversion in both Sencar and SKH-1 mice. In general, the rate of malignant conversion was faster in UVB-induced tumors compared with DMBA-induced tumors. The relative efficacy of each agent was similar in both groups and was in the order: acetone less than TPA less than BPB less than BPO less than ABP. Our data suggest that free-radical-generating compounds may accelerate the malignant conversion of benign papillomas into carcinoma, indicating that epigenetic mechanism(s) may also be involved in this process.
Athar
M
M
Department of Dermatology Skin Diseases Research Center, University Hospitals of Cleveland, OH.
Lloyd
J R
JR
Bickers
D R
DR
Mukhtar
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000096:Acetone / Q000633:toxicity*; D000578:Amidines / Q000633:toxicity*; D000818:Animals; D001585:Benzoyl Peroxide / Q000633:toxicity*; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic; D005260:Female; D005609:Free Radicals; D051379:Mice; D008812:Mice, Hairless; D008815:Mice, Inbred Strains; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D010212:Papilloma / Q000473:pathology*; D010545:Peroxides / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014466:Ultraviolet Rays; D020122:tert-Butylhydroperoxide
D000578:Amidines; D002273:Carcinogens; D005609:Free Radicals; D010545:Peroxides; D000096:Acetone; D015127:9,10-Dimethyl-1,2-benzanthracene; C046728:2,2'-azobis(2-amidinopropane); D020122:tert-Butylhydroperoxide; D013755:Tetradecanoylphorbol Acetate; D001585:Benzoyl Peroxide