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The Protective Effect of Estradiol-17ß against Polycyclic Hydrocarbon Cytotoxicity¹

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461

7,12-Dimethylbenz(a)anthracene (DMBA) (10^-6 M) inhibited the growth of cultured epithelial rat liver cells and depressed thymidine-³H incorporation. In a series of methyl- and ethyl-substituted benz(a)anthracenes there was significant correlation between the reported carcinogenicity of the derivative and its capacity to inhibit acidinsoluble thymidine-³H incorporation. Similar results were obtained with a diploid strain of rat lung fibroblasts, but a human cancer cell (HeLa) and a rat hepatoma (HTC) were insensitive to the cytotoxic effect of DMBA.

In contrast to DMBA, a series of diazo dyes of varying hepatocarcinogenicities did not significantly inhibit thymidine-³H incorporation by liver epithelial cell cultures.

Estradiol-17ß at 10^-6 M protected liver and breast epithelial cultures from the inhibitory effect of DMBA on thymidine-³H incorporation. The other steroids tested had little or no protective effect at 4 x 10^-5 M. The possible relationship of this protective effect of estradiol-17ß to clinical and epidemiological data in women is discussed.

¹ This investigation was supported by NIH Grant CA-AI-11992, NSF Grant GB 24175A, and American Cancer Society Grant VC-33F.

² Research Associate, supported by NIH Grant CA-AI 11992. Present address: The Fels Research Institute and Department of Microbiology, Temple University School of Medicine, Philadelphia, Pa. 19140.

Received 9/20/72. Accepted 6/27/73.