These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Aberrant and nonrandom methylation of chromosomal DNA-binding proteins of colonic epithelial cells by 1,2-dimethylhydrazine.
    Author: Boffa LC, Gruss RJ, Allfrey VG.
    Journal: Cancer Res; 1982 Feb; 42(2):382-8. PubMed ID: 6895714.
    Abstract:
    The alkylating carcinogen 1,2-dimethylhydrazine (DMH) induces colonic tumors with high incidence. The sites of in vivo modification of target macromolecules were studied using [methyl-3H]DMH. Carcinogen binding to subcellular fractions of colonic epithelial cells was analyzed at time intervals ranging from 10 min to 36 hr, with particular emphasis on the alkylation of nuclear constituents. DMH modifies not only nucleic acids but also histones and other DNA-binding proteins in the target cells. Separation of the 3H-methylated amino acids showed aberrant methylation patterns after exposure to [3H]DMH, as compared with methylations observed with [methyl-3H]methionine as a natural methyl group donor. DMH-modified histone H1 contained methylated lysin, arginine, and histidine residues not normally found, and other histones had abnormal methylarginine contents. High-mobility-group proteins and other nuclear proteins contained methyllysine residues not normally detected. Proteins known to be associated with template-active and more accessible DNA sequences, such as the high-mobility group proteins and the multiacetylated forms of histones H3 and H4, were preferentially damaged after exposure to [3H]DmH. The result suggests that carcinogen-induced chromosomal damage is not random and may selectively affect proteins in the actively transcribing or replicating genes in the target cells. That damage affects the amino acids most likely to be involved in DNA binding.
    [Abstract] [Full Text] [Related] [New Search]