Further investigations into the effect of non-benzo ring bay-region methyl substituents on tumor-initiating activity of polycyclic hydrocarbons

Cancer Lett. 1987 Sep;36(3):317-24. doi: 10.1016/0304-3835(87)90025-5.


The effect of a methyl substituent at the non-benzo ring bay-region position of benzo[e]pyrene (B[e]P), cholanthrene (CA) and dibenz[a,j]anthracene (DB[a,j]A) on skin tumor-initiating activity was examined. A methyl substituent at the 1-carbon of B[e]P enhanced tumor-initiating activity of the parent compound (0.18 vs. 2.4 papillomas/mouse for B[a]P vs. 1-methyl-B[e]P, respectively, with an 800 nmol initiating dose). A methyl substituent at the 7- and 14-carbons of DB[a,j]A increased the activity of this weak initiator more than 13 times. The introduction of a methyl substituent at the non-benzo ring bay-region position of CA (i.e. carbon atom 6) dramatically increased tumor-initiating activity in SENCAR mice. 6-Methyl-CA was found to be a more potent skin tumor-initiator than 3-methyl-CA, and nearly as potent as 7,12-dimethylbenz[a]anthracene, one of the most potent initiators yet tested in the 2-stage initiation-promotion mouse skin model. When taken together with previous results from our laboratories, the data further support the generality of the enhancing effect of a non-benzo ring bay-region methyl substituent on polycyclic hydrocarbon tumor-initiation.

Publication types

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

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Benz(a)Anthracenes / toxicity*
  • Benzo(a)pyrene / toxicity*
  • Benzopyrenes / toxicity
  • Carcinogens
  • Female
  • Methylcholanthrene / analogs & derivatives
  • Methylcholanthrene / toxicity
  • Mice
  • Papilloma / chemically induced*
  • Skin Neoplasms / chemically induced*
  • Structure-Activity Relationship


  • Benz(a)Anthracenes
  • Benzopyrenes
  • Carcinogens
  • 6-methylcholanthrene
  • Benzo(a)pyrene
  • cholanthrene
  • Methylcholanthrene
  • 9,10-Dimethyl-1,2-benzanthracene
  • 7,14-dimethyldibenz(a,j)anthracene
  • 1-methylbenzo(e)pyrene