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Related Experiment Videos

Genetic determinant and environmental carcinogens

M Nagao1, M Ochiai, T Ushijima

  • 1Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan. mnagao@gan2.ncc.go.jp

Mutation Research
|July 24, 1998
PubMed
Summary

Genetic factors influence susceptibility to colon cancer induced by 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a common mutagen in cooked foods. F344 rats showed dominant inheritance for PhIP-induced aberrant crypt foci, suggesting a genetic basis for colon cancer risk.

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Area of Science:

  • Toxicology
  • Genetics
  • Carcinogenesis

Background:

  • 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a prevalent mutagenic heterocyclic amine in cooked foods.
  • PhIP is linked to colon cancer induction in rats and suspected in human colon carcinogenesis.

Purpose of the Study:

  • To investigate the ecogenetics of PhIP-induced colon carcinogenesis using aberrant crypt focus (ACF) formation as a biomarker.
  • To identify genetic factors contributing to differential susceptibility to PhIP-induced colon cancer.

Main Methods:

  • Utilized four rat strains (BUF, BN, F344, ACI) to assess PhIP-DNA adducts and ACF formation.
  • Analyzed F1 progenies and backcrosses to determine inheritance patterns of ACF susceptibility.
  • Employed simple sequence length polymorphism (SSLP) and representational difference analysis (RDA) for chromosomal mapping.

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Main Results:

  • F344 rats exhibited lower PhIP-DNA adduct levels but high ACF numbers, indicating no direct correlation between adducts and ACF formation.
  • Susceptibility to PhIP-induced ACF in F344 rats was autosomally dominant over ACI rats.
  • BUF rats possess at least two genes influencing ACF formation, with complex dominant and recessive inheritance patterns.

Conclusions:

  • Colon cancer susceptibility to PhIP is genetically determined, with specific genes influencing ACF formation.
  • Understanding these genetic factors can aid in identifying high-risk human populations for early cancer prevention.
  • Chromosomal mapping of susceptibility genes is crucial for targeted cancer prevention strategies.