Inhibition of the tumor-initiating ability of the potent carcinogen 7,12-dimethylbenz(a)anthracene by the weak tumor initiator 1,2,3,4-dibenzanthracene.

Abstract

ARyl hydrocarbon hydroxylase (AHH) in mouse epidermis was inducible by topical application of several tumor-initiating polycylic 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).

• Authors: T J Slaga, R K Boutwell
• Journal: Cancer research (Cancer Res) Vol. 37 Issue 1 Pg. 128-33 (Jan 1977) ISSN: 0008-5472 [Print] United States
• PMID: 401469 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benz(a)Anthracenes
• 9,10-Dimethyl-1,2-benzanthracene
• DNA
• Aryl Hydrocarbon Hydroxylases

Topics

• 9,10-Dimethyl-1,2-benzanthracene (antagonists & inhibitors, metabolism)
• Animals
• Aryl Hydrocarbon Hydroxylases (biosynthesis)
• Benz(a)Anthracenes (antagonists & inhibitors, metabolism, pharmacology, toxicity)
• Binding, Competitive
• Carcinoma (chemically induced)
• DNA (metabolism)
• Enzyme Induction (drug effects)
• Female
• In Vitro Techniques
• Mice
• Neoplasms, Experimental (chemically induced)
• Papilloma (chemically induced)
• Skin (metabolism)
• Skin Neoplasms (chemically induced)