Effects of Acute and Subchronic Exposure of Topically Applied Fullerene Extracts on the Mouse Skin

Abstract

The recent discovery that fullerenes (C60) can be produced in macroscopic quantities has sparked much interest in the chemistry of this unusual molecule. Concerns have also arose about the potential carcinogenic effects of this molecule. We have addressed the potential acute and subchronic toxic effects of fullerenes applied in benzene on the mouse skin. The acute toxic effects measured in this study included epidermal DNA synthesis and the induction of ornithine decarboxylase activity in the epidermis. At the topical dose of fullerenes used in these studies (i.e., 200 ug), we found no effect on either DNA synthesis or ornithine decarboxylase activity over a 72 hour time course after treatment. The subchronic effects of the fullerenes as a mouse skin tumor promoter was assessed by repeatedly applying the chemical to the skin after initiation with the polycyclic aromatic hydrocarbon, 7,12-dimethlybenz-anthracene (DMBA). Repeated administration of the fullerenes for up to 24 weeks post-initiation did not result in either benign or malignant skin tumor formation, whereas promotion with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the formation of benign skin tumors. Our data indicate that fullerenes applied in benzene at a likely industrial exposure level do not cause acute toxic effects on the mouse skin epidermis.

Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60)

“…In accordance with the inability of C 60 to produce ROS unless exposed to a strong light source, many classical toxicity studies have failed to demonstrate significant acute or sub-acute in vivo toxicity, genotoxicity or in vitro cytotoxicity of various C 60 preparations applied at relatively large concentrations [78][79][80][81][82][83][84][85]. However, the perception of C 60 as relatively non-toxic contradicts the surprising demonstration by Sayes et el.…”

Novel harmful effects of [60]fullerene on mouse embryos in vitro and in vivo

“…This recent result also supports our suggestion. Therefore, it is recommended that women avoid exposure to C60 especially during pregnancy, although its in vivo tumor-promoting results showed a negative response [13].…”

Tissue Sites of Uptake of14C-Labeled C60

“…To date, none of these risks have been substantiated. In fact, topically applied fullerenes (unfunctionalized C 60 and C 70 ) did not exhibit tumor-promoting activity in the classic 7,12-dimethylbenzanthracene-initiated mouse skin model, or cause acute toxicity in mouse skin as measured by epidermal DNA synthesis and the induction of ornithine decarboxylase activity (7). Most biological studies of fullerenes have focused on water-soluble C 60 derivatives, and several potentially interesting biological properties have been reported.…”