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The Interaction of 7,12-Dimethylbenz(a)anthracene with Cells Sensitive and Resistant to Toxicity Induced by This Carcinogen

The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, and McArdle Laboratory, University of Wisconsin Medical School, Madison, Wisconsin 53706

The multiplication of monolayer cultures of transformed rodent cells and normal or transformed human cells was not inhibited by concentrations of 7,12-dimethylbenz(a)anthracene (DMBA) 200–500 times greater than those that inhibited the multiplication of normal embryonic rodent cells. Fluorescence microscopy showed that DMBA localized to about the same degree within the cytoplasm of cells that were sensitive or resistant to the toxic effect of the carcinogen. Autoradiography with DMBA-³H and an aqueous cell fixative (formalin) revealed that the carcinogen was distributed throughout the cytoplasm and nucleus and that the concentrations were similar in sensitive and resistant cells. However, when the cells were treated with a fixative in which DMBA is soluble (Carnoy's), most (90%) of the labeled compound was eliminated from the resistant cells whereas a considerable amount appeared to be bound within both the cytoplasm and the nucleus of sensitive cells. The difference in the binding of DMBA by the 2 types of cells was confirmed by isolating and assaying for radioactivity individual cellular constituents after cells had been exposed to DMBA-³H. Sensitive cells bound 10–50 times more DMBA to their nucleic acids and protein than did resistant cells. With mouse embryo cells, the amount of DMBA bound to DNA and protein was proportional to the growth-inhibitory effect of the carcinogen within the dose range 0.01–0.1 µg/ml.

¹ Supported in part by USPHS Research Grant No. CA 04534-08 from the National Cancer Institute and Research Grant No. E-89 from the American Cancer Society awarded to The Wistar Institute.

² Leukemia Society Scholar and Department of Pathology, University of Pennsylvania.

³ Recipient of an Eleanor Roosevelt International Cancer Fellowship of The American Cancer Society awarded by the International Union Against Cancer. Permanent address: Chester Beatty Research Institute, London, England.

Received 8/15/66. Accepted 12/29/66.