Lack of initiating capacity of the genotoxic air pollutant 2-nitrofluorene in the mouse skin two-stage carcinogenesis system.
2-Nitrofluorene (NF) is a potent genotoxic substance found in environments where incomplete combustion takes place. NF is a mutagen and a carcinogen in animal models. NF or 7,12-dimethylbenz[a]anthracene (DMBA) was administered once topically to female SENCAR mice followed by promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in two different studies. TPA (2-5 micrograms) was administered twice a week for 13 or 19 weeks after initiation of DMBA (5-10 micrograms) or NF (50-1500 micrograms). DMBA administration (positive control) resulted in the formation of many papillomas, which were seen from week 8-9 after initiation. The negative controls administered acetone only were free of tumours. NF administration did not result in papilloma formation, even at high initiating doses of NF combined with a dose of TPA causing a systemic toxic effect in terms of a significant reduced body weight. The mechanism behind the absence of papilloma formation after administration of genotoxic and carcinogenic NF remains to be investigated.
Möller
L
L
Unit for Analytical Toxicology, Karolinska Institute, NOVUM, Huddinge, Sweden.
Zeisig
M
M
Toftgård
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D003043:Cocarcinogenesis; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D010212:Papilloma / Q000139:chemically induced*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate
D000393:Air Pollutants; D005449:Fluorenes; C019499:2-nitrofluorene; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate