In-vivo carcinogenicity of 2-nitro-oxaphenalenes.
2-Nitro-oxaphenalenes are synthetic chemicals which were synthesized in the authors' laboratory. They are the most efficient mutagenic compounds on mammalian cells in culture. They are chemically related to the nitro-naphthofuran family by the displacement of the heterocycle on the naphthalene ring. Since nitro-naphthofurans have a strong mutagenic activity in bacterial tests without metabolic activation and are active in-vivo carcinogens, the purpose of this study was to demonstrate the carcinogenic activity of two 2-nitro-oxaphenalenes. The two compounds were injected s.c. into Wistar rats initially 6-weeks-old. They were dissolved in dimethylsulfoxide (DMSO) at a concentration of 1 mg/ml. A s.c. injection of 0.5 ml containing 0.5 mg of carcinogen was given once a week in the neck of each animal tested. Five control animals were not injected and five animals received 0.5-ml injection of DMSO every week to serve as a control. The animals developed tumors only at the site of injection. The tumors were classified as high grade fibrosarcomas. This experiment demonstrates that: (i) 2-nitro-oxaphenalenes are very active in-vivo carcinogens in rats; (ii) there is a good correlation between the high mutagenic activity especially in mammalian tests and the strong carcinogenicity of the compounds; and (iii) the presence of a 6-methoxy group increases by two-fold the carcinogenic potential.
Salmon
R J
RJ
Service de chirurgie (Section Médicale et Hospitalière), Institut Curie, Paris, France.
Buisson
J P
JP
Hendrickx
B
B
Vielh
P
P
Aussepe
L
L
Moens
W
W
Royer
R
R
D000818:Animals; D002273:Carcinogens; D002470:Cell Survival / Q000187:drug effects; D005354:Fibrosarcoma / Q000139:chemically induced*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity*; D009284:Naphthols / Q000633:toxicity*; D009581:Nitrofurans / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D002273:Carcinogens; D009153:Mutagens; D009284:Naphthols; D009581:Nitrofurans; C059442:2-nitronaphtho(1,8-bc)pyran; C059441:6-methoxy-2-nitronaphtho(1,8-bc)pyran; C053501:2-nitronaphtho(2,1-b)furan; C030911:2-nitro-7-methoxynaphtho(2-1b)furan