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The tumorigenicity of mutagenic contact-sensitizing chemicals

R E Albert1, P S Magee

  • 1Department of Environmental Health, University of Cincinnati Medical Center, OH 45267-0056, USA. albertre@email.uc.edu

Risk Analysis : an Official Publication of the Society for Risk Analysis
|August 19, 2000
PubMed

Insights

Some chemicals causing allergic contact dermatitis (ACD) may also be genotoxic, leading to cancer. Research suggests 20-28% of contact sensitizers are mutagenic and tumorigenic, potentially identifying around 90 such chemicals.

Area of Science:

  • Toxicology
  • Dermatology
  • Carcinogenesis

Background:

  • Electrophilic chemicals can cause allergic contact dermatitis (ACD) by adducting proteins.
  • Electrophiles are also implicated in mutagenicity and carcinogenicity through DNA adduct formation.
  • A shared electrophilic mechanism suggests overlap between contact sensitizers and genotoxic carcinogens.

Purpose of the Study:

  • To investigate the potential for contact sensitizers to be genotoxic tumorigens.
  • To analyze structure-activity relationships for contact sensitization among known genotoxic chemicals.

Main Methods:

  • Evaluation of 146 chemicals bioassayed for tumorigenicity and mutagenicity by the National Toxicology Program.
  • Analysis of structure-activity relationships for contact sensitization.

Main Results:

  • The proportion of contact sensitizers that were both mutagenic and tumorigenic ranged from 20% to 28%.
  • This suggests approximately 90 genotoxic tumorigens among 384 validated human contact sensitizers.

Conclusions:

  • A significant subset of contact sensitizers may possess genotoxic carcinogenic potential.
  • The electrophilic nature of chemicals is a key factor linking ACD and genotoxicity.
  • Further investigation is warranted to identify and manage these dual-acting chemicals.

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