Changing responsiveness to all-trans retinoic acid of rat tracheal epithelial cells at different stages of neoplastic transformation

Carcinogenesis
D J FitzgeraldP Nettesheim

Abstract

Retinoic acid (RA) treatment of rat tracheal epithelial (RTE) cells, pre-exposed to the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), inhibited transformation in a dose-dependent manner. Treatment with RA at concentrations ranging from 3-33 nM reduced the MNNG-induced transformation frequencies by 13-81% and in some experiments by greater than 90%. RA treatment for only 3 days caused 65-75% inhibition of transformation; treatments of longer duration resulted in greater inhibition of transformation. Delaying the onset of RA treatment reduced its effectiveness, but even when RA treatment was delayed for 3 weeks following MNNG exposure, 60% inhibition still occurred. The inhibition of transformation appeared to be irreversible. The colony forming efficiency of cells isolated from transformed colonies 5 weeks after MNNG exposure was drastically reduced when the replated cells were treated with RA either 1 day or 4 days after plating, indicating that RA blocked cell replication. However, cells isolated from transformed colonies at later times after MNNG exposure were increasingly resistant to the antiproliferative effects of RA. The RA concentration causing 50% inhibition (RA-IC50) of colony formation was 0.1...Continue Reading

Citations

Jan 1, 1991·Journal of Cancer Research and Clinical Oncology·L R CoxS J Garte
Nov 1, 1987·Environmental Health Perspectives·P NettesheimT E Gray
Oct 1, 1991·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·T GrayP Nettesheim
Apr 1, 1988·Molecular and Cellular Biology·T D HalazonetisP Leder

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