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Inhibition of the Tumor-initiating Ability of the Potent Carcinogen 7,12-Dimethylbenz(a)anthracene by the Weak Tumor Initiator 1,2,3,4-Dibenzanthracene¹

Cancer and Toxicology Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 [T. J. S.], and McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706 [R. K. B.]

Aryl hydrocarbon hydroxylase (AHH) in mouse epidermis was inducible by topical application of several tumor-initiating polycyclic aromatic hydrocarbons. The weak tumor initiator 1,2,3,4-dibenazanthracene (1,2,3,4-DBA), at dose level of 200 nmoles, increased AHH activity more than 10-fold over that of the acetone controls at 12 hr after treatment. Administration of the same quantity of the potent initiator 7,12-dimethylbenz(a)anthracene (DMBA) increased AHH activity approximately 4-fold over that of the control at 12 hr after treatment. Simultaneous treatment with 200 or 100 nmoles of DMBA and 1,2,3,4-DBA resulted in AHH activity that was 546 and 732% that of the controls, respectively, 12 hr after treatment; this was less AHH activity than was observed when 1,2,3,4-DBA was administered alone. Doses of 20 nmoles or more of 1,2,3,4-DBA, when given at about the same time as DMBA, effectively inhibited DMBA initiation of skin tumors in a two-stage system of tumorigenesis. The results suggest that the weak initiator 1,2,3,4-DBA may program the epidermal AHH system to metabolize the strong carcinogen DMBA to noncarcinogenic intermediate(s).

¹ Supported by NIH Grants CA17605, CA07175, and CA05002 and by the U. S. Energy Research and Development Administration under contract with the Union Carbide Corporation.

Received 7/19/76. Accepted 10/ 7/76.