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An in Vitro and in Vivo Investigation of Three Surface-active Agents as Modulators of Cell Proliferation

Miami Valley Laboratories, The Procter & Gamble Company, Cincinnati, Ohio 45247

The effects of three surface-active compounds including one cationic surfactant, docosyldimethyl-2-hydroxyethylammonium bromide (C₂₂-AE), and two zwitterionic surfactants, 11-tetradecyldimethylammonio-3,6,9-trioxaundecanoate (C₁₄-ATOU) and 26-tetradecyldimethylammonio-3,6,9,12,15,18,21,24-octaoxahexacosylsulfate (C₁₄-AE₉-S), on the growth of 11 tumorigenic and nontumorigenic hamster and murine cell lines were investigated. For the most part, the lytic and growth-inhibitory abilities of these surfactants were found to be significantly more dependent upon the surfactant structure than upon the cell type investigated. The cationic surfactant, C₂₂-AE, was much more cytotoxic than the two zwitterionic surfactants, C₁₄-ATOU and C₁₄-AE₉-S. C₁₄-AE₉-S was somewhat more cytotoxic than C₁₄-ATOU. None of the tumorigenic cells were more sensitive to treatment with C₂₂-AE or C₁₄-AE₉-S than were their nontumorigenic counterparts. However, one tumorigenic cell type, a strain of benzo(a)pyrene-transformed hamster cells, was 20 times more sensitive to treatment with C₁₄-ATOU than were the nontransformed hamster cells. The sensitivity of these tumorigenic cells towards C₁₄-ATOU is not due to an increased uptake of surfactant relative to other cell types nor is it due to the observed difference in the ability of these cells to metabolize the compound.

Despite the selective cytotoxicity of C₁₄-ATOU in vitro for one strain of benzo(a)pyrene-transformed hamster cells, this surfactant was not efficacious in vivo against P388 leukemia, Lewis lung carcinoma, or C26 adenocarcinoma at the doses tested. Thus, no correlation can be made between the observation of differential growth control in vitro and antitumor activity in vivo. We propose that this lack of correlation between in vitro and in vivo data is the result of the unique sensitivity of the benzo(a)pyrene-transformed cells to this surfactant. However, the possibility that the observed lack of correlation between in vitro data and in vivo data may be due to a problem in delivery of the compound is discussed.

¹ Present address: Yale University School of Medicine, New Haven, Conn. 06520.

² To whom requests for reprints should be addressed.

Received 10/11/79. Accepted 1/ 2/80.