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The Effects of 7,12-Dimethylbenz()anthracene on the Synthesis of Nucleic Acids in Rapidly Dividing Hepatic Cells in Rats¹

Division of Pharmacology, Sloan-Kettering Institute for Cancer Research, New York, New York 10021

Single i.v. doses of 7,12-dimethylbenz()anthracene cause transient suppression of the growth of regenerating liver in partially hepatectomized rats for about 24 hr, as shown by decrease in mitotic index and inhibition of increases of cell number and total DNA. Similar doses inhibit the incorporation of thymidine-2-¹⁴C and orthophosphate-³²P into DNA of regenerating liver and rapidly growing liver in intact immature rats. The inhibition is evident within 2 hr, maximal by 6 to 8 hr, and no longer present at 24 hr. It is dose dependent and not prevented by adrenalectomy. The incorporation of orotic acid-6-¹⁴C into nRNA is unaffected. The findings are consistent with a suggestion that 7,12-dimethylbenz()anthracene affects DNA primarily in cells in the S phase of the mitotic cycle, possibly by binding to the macromolecule and thus inhibiting its synthesis. This effect may be related to carcinogenic activity.

¹ Aided by Grant CA 08748 from the National Cancer Institute, USPHS.

² Visiting Research Fellow from the Pharmacological Institute of the University of Cologne, Germany.

Received 12/29/69. Accepted 3/25/70.