This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanaka, N. Articles by Barrett, J. C. Search for Related Content PubMed PubMed Citation Articles by Tanaka, N. Articles by Barrett, J. C.

2,3,7,8-Tetrachlorodibenzo-p-dioxin Enhancement of N-Methyl-N'-nitro-N-nitrosoguanidine-induced Transformation of Rat Tracheal Epithelial Cells in Culture

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

The abilities of various dioxins to induce toxicity or transformation of rat tracheal epithelial cells in culture were examined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was not cytotoxic and did not induce transformation as measured by the induction of growth-altered, preneoplastic cells (termed enhanced growth variants). However, TCDD enhanced the transformation of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat tracheal epithelial cells. Other dioxin congeners with 0 to 3 chloro substitutions were inactive in enhancing MNNG transformation. TCDD was most effective at a concentration of 0.3 nM and when treatment was administered immediately after MNNG exposure. The dose-response curves for enhancement of MNNG-induced transformation and induction of aryl hydrocarbon hydroxylase activity by TCDD were similar. These results are consistent with the hypothesis that the enhancement of cell transformation by TCDD is mediated through the TCDD receptor. TCDD also enhanced transformation when the cells were treated before MNNG treatment. The ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) to enhance MNNG-induced rat tracheal epithelial transformation was also examined. In contrast to the findings with TCDD, the number of transformed colonies was increased only by pretreatment with TPA followed by MNNG. TPA-pretreatment enhanced equally the number of normal cells forming colonies and the total number of transformed colonies after selection; therefore, the transformation frequency (transformants per total surviving colonies) was unchanged by TPA. In contrast, TCDD treatment enhanced the transformation frequency in MNNG-exposed cultures since the number of transformed colonies increased while the number of total colonies remained constant. Thus, TCDD appears to act by a different mechanism than TPA. TCDD enhancement of MNNG-induced transformation may be attributed to a promotional effect, a comutagenic action, or a modulation of cell proliferation and/or differentiation mediated through the TCDD receptor.

¹ Present address: Department of Cell Biology, Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257, Japan.

² To whom requests for reprints should be addressed.

Received 10/14/88. Revised 2/14/89. Accepted 2/17/89.

This article has been cited by other articles:

				J. M. Martinez, C. A. Afshari, P. R. Bushel, A. Masuda, T. Takahashi, and N. J. Walker Differential Toxicogenomic Responses to 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Malignant and Nonmalignant Human Airway Epithelial Cells Toxicol. Sci., October 1, 2002; 69(2): 409 - 423. [Abstract] [Full Text] [PDF]