Initiating, promoting and carcinogenic activities of three naphthofurans in a mouse skin long-term study

The initiating, promoting and carcinogenic activities of three naphthofurans, 2-nitro-7-methoxynaphto[2,1-b]furan (A), 2-nitronaphtho[2,1-b]furan (C) and 7-methoxynaphtho[2,1-b]-furan (E), were determined in a long-term assay using CD1 mice, by means of a two-step skin painting regimen. Compound A was a strong initiator and a weak carcinogen, and compound C was a strong promotor and a moderate carcinogen, whereas compound E did not have any effect. The NO2 group at the 2 position on the molecule was concluded to be responsible for the carcinogenic activity of the former two naphthofurans. The addition of a CH3O group at position 7 enhanced the initiating ability while it diminished the promoting and carcinogenic potentials. These findings indicate that the initiating activity is closely linked to the mutagenic potential previously detected in in vitro and in vivo mammalian cell systems, while the promoting and carcinogenic activities are related to the effects detected in mouse short-term skin tests.