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

Cancer Res. 1977 Jan;37(1):128-33.

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).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / antagonists & inhibitors*
  • 9,10-Dimethyl-1,2-benzanthracene / metabolism
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Benz(a)Anthracenes / antagonists & inhibitors*
  • Benz(a)Anthracenes / metabolism
  • Benz(a)Anthracenes / pharmacology*
  • Benz(a)Anthracenes / 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*

Substances

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