TUMORIGENIC ACTIVITY OF FLUORANTHENE, 2-METHYLFLUORANTHENE AND 3-METHYLFLUORANTHENE IN NEWBORN CD-1 MICE

Fluoranthene (FA) is frequently among the more abundant components det ected in environmental mixtures of polycyclic aromatic hydrocarbons. S everal 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 tu mors in newborn mice. Among the five isomers of methylfluoranthene, on ly 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 mu mol. The bioassay was terminated when mice w ere 1 year old. At a dose of 17.3 mu mol, FA and 2-MeFA induced a simi lar incidence of lung tumors (65-96%) in both male and female mice. Ho wever, tumor multiplicity in the lung was different between FA and 2-M eFA. At a dose of 17.3 mu mol, the multiplicity of lung tumors observe d for mice administered 2-MeFA ranged from 3.04 to 3.94 tumors per mou se. 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 sign ificant incidence of lung tumors in either male or female mice. All th ree compounds when administered to newborn mice did induce a significa nt incidence of liver tumors among male mice. The relative tumorigenic potency observed was FA greater than or equal to 2-MeFa >> 3-MeFA. On ly 2-MeFA at a dose of 17.3 mu mol was tumorigenic in the liver of fem ale mice. These bioassay results are contrasted with prior studies on the in vitro genotoxic activity and metabolic activation pathways of F A, 2-MeFA and 3-MeFA.