Comitogenic activity of n‐alkane and related tumor promoters in murine lymphocytes

Abstract

AbstractLinear alkanes of specific chain length were found to enhance differentially the mitogenic response of murine spleen lymphocytes to the lectin phytohemagglutinin. Within the homologous series of compounds having between six and eighteen carbon atoms, a biphasic structure–function relationship was found, with maximum comitogenic activity occurring for tetradecane, and none or little for octane and octadecane. No alkane was mitogenic per se, and no alkane displaced the optimum mitogenic concentration of the lectin. The concentration of tetradecane having equivalent comitogenic activity was similar to that of methyl myristate, a simple alkyl ester of equal alkyl chain length, but approximately four orders of magnitude less that of the potent promoter 12‐0‐tetradecanoylphorbol‐13‐acetate (TPA). A similar ratio of potencies of TPA and the alkane dodecane, also a lymphocyte comitogen, has previously been found for promotion of mouse epidermal tumorigenesis. Maximum comitogenic activity was found when alkane and lectin were added to cultures simultaneously, the effect decreasing sharply when alkane addition was delayed relative to lectin. These findings suggest the existence of a cellular receptor with specificity for hydrophobic functions with chain lengths lying within a restricted range. Binding to this receptor also appears to be a common early event in tumor promotion, comitogenicity, and comutagenicity by agents of several chemical types.