N-alkanes with intermediate (8-20) carbon chain lengths are frequent constituents of fossil fuels, their fractions, pyrolysis products and domestic preparations, and as such are present in many products to which occupational and general populations are exposed. Although tumor-promoting activity has been documented for agents of this class, and in fact may be the determining factor in carcinogenesis by products which contain them, little effort has been made to determine their mechanism of action, and whether it resembles that of other more extensively studied phorbol diester promoters. The studies which have been performed to date have not been carried out in highly sensitive (SENCAR) strains, moreover, which have been invaluable for identifying agents which block skin carcinogenesis and hence indicate mechanisms of action, and demonstrating its resolution into up to four stages. The promoting activity of n-alkanes requires much higher doses than that of phorbol diester promoters, suggesting that, like the agent mezerein, these agents may be most active specifically in one stage of promotion.
The aim of this project is therefore to study the tumor-promoting activity of the n-alkane n-dodecane in SENCAR mice initiated with 7,12-dimethylbenz(a)anthracene, with respect to: A. The dose of alkane B. Activity in stage I or II of promotion. Two stage promotion will be carried out: i) With alkane as first, and mezerein as second stage promoter. ii) With TPA (1 dose) as first, and alkane as second stage promoter. C. Modification by antipromoting agents with specific activity for individual stages of promotion: i) All trans - retinoic acid ii) Tosylphenylalanine chloromethyl ketone, a protease inhibitor D. Modification by the specific protease inhibitor leupeptin, and the specific ornithine decarboxylase inhibitor Alpha,Alpha-difluoromethylornithine.
| Baxter, C S; Andringa, A; Chalfin, K et al. (1991) Effect of tumor-promoting agents on density and morphometric parameters of mouse epidermal Langerhans and Thy-1+ cells. Carcinogenesis 12:1017-21 |
| Baxter, C S; Andringa, A; Chalfin, K et al. (1989) Comparative histomorphometric changes in SENCAR mouse epidermis in response to multiple treatments with complete and stage-specific tumor promoting agents. Carcinogenesis 10:1855-61 |
