Tumorigenic activity of fluoranthene, 2-methylfluoranthene and 3-methylfluoranthene in newborn CD-1 mice.
Fluoranthene (FA) is frequently among the more abundant components detected in environmental mixtures of polycyclic aromatic hydrocarbons. Several methylated fluoranthenes, although less prevalent than FA, have also been detected as environmental pollutants. While FA is inactive as a tumorigenic agent on mouse skin, it does induce lung and liver tumors in newborn mice. Among the five isomers of methylfluoranthene, only 2-methylfluoranthene (2-MeFA) and 3-methylfluoranthene (3-MeFA) are active as tumor initiators on mouse skin. A comparative bioassay was performed to determine the relative tumorigenic activity of FA, 2-MeFA and 3-MeFA in newborn CD-1 mice. All three compounds were assayed at doses of 3.46 and 17.3 mumol. The bioassay was terminated when mice were 1 year old. At a dose of 17.3 mumol, FA and 2-MeFA induced a similar incidence of lung tumors (65-96%) in both male and female mice. However, tumor multiplicity in the lung was different between FA and 2-MeFA. At a dose of 17.3 mumol, the multiplicity of lung tumors observed for mice administered 2-MeFA ranged from 3.04 to 3.94 tumors per mouse. In contrast, animals treated with FA developed only an average of 1.12-2.45 tumors per mouse. 3-MeFA did not induce a statistically significant incidence of lung tumors in either male or female mice. All three compounds when administered to newborn mice did induce a significant incidence of liver tumors among male mice. The relative tumorigenic potency observed was FA > or = 2-MeFa >> 3-MeFA. Only 2-MeFA at a dose of 17.3 mumol was tumorigenic in the liver of female mice. These bioassay results are contrasted with prior studies on the in vitro genotoxic activity and metabolic activation pathways of FA, 2-MeFA and 3-MeFA.
LaVoie
E J
EJ
Department of Pharmaceutical Chemistry, Rutgers, State University of New Jersey, College of Pharmacy, Piscataway 08855.
Cai
Z W
ZW
Meschter
C L
CL
Weyand
E H
EH
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000139:chemically induced; D000818:Animals; D000831:Animals, Newborn; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy
D002273:Carcinogens; D005449:Fluorenes; C035918:3-methylfluoranthene; C035917:2-methylfluoranthene; C007738:fluoranthene