Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules

Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non‐enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried out in the authors' laboratory. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Wiley

Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules

Cancer, Volume 47 (10) – Mar 15, 1982

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Publisher
Wiley
Copyright
"Copyright © 1981 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0008-543X
eISSN
1097-0142
D.O.I.
10.1002/1097-0142(19810515)47:10<2327::AID-CNCR2820471003>3.0.CO;2-Z
Publisher site
See Article on Publisher Site

Abstract

Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non‐enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried out in the authors' laboratory.

Journal

CancerWiley

Published: Mar 15, 1982

References

  • Cancer prevention as a realizable goal
    Berenblum, I
  • Liver microsomal metabolism of aflatoxin B1 to a reactive derivative toxic to Salmonella typhimurium TA 1530
    Garner, RC; Miller, EC; Miller, JA
  • Chemical carcinogens and DNA
    Maher, VM; McCormick, JJ
  • Toxicity of pyrrolizidine alkaloids
    Mattocks, AR
  • The detection of carcinogens as mutagens in the Salmonella microsome test: Assay of 300 chemicals
    McCann, J; Choi, E; Yamasaki, E; Ames, BN
  • In vivo combinations between carcinogens and tissue constituents and their possible role in carcinogenesis
    Miller, EC; Miller, JA
  • Chemical structure and carcinogenicity of aliphatic hydrazo, azo, and azoxycompounds and of triazenes, potential in vivo alkylating agents
    Preussmann, R; Druckrey, H; Ivankovic, S; von Hodenberg, A

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