Molecular aspects of chemical carcinogenesis: the roles of oncogenes and tumour suppressor genes

Toxicology. 1995 Feb 27;96(3):173-94. doi: 10.1016/0300-483x(94)02991-3.

Abstract

The observation that oncogenes are frequently activated in human tumours raises the question of whether these genes are involved in chemical carcinogenesis. H-ras activation is probably an initiating event in mouse skin and rat mammary gland systems. The H-ras oncogene is also important in mouse liver tumours; in mouse lung the K-ras gene is commonly activated. In both, the mutations observed are usually those predicted from the adduct-forming properties of the carcinogen. Among non-ras oncogenes, only raf and neu have been detected in experimental tumours. Tumour suppressor genes are frequently inactivated in human tumours. Searches for such phenomena in animal tumours have generally had disappointing results. p53 and Rb gene alterations are rarely observed in chemically-induced tumours. The reason may be that unknown tumour suppressor genes are involved in animal tumour development. Several novel genes have been identified using animal tumour susceptibility models. Thus, ras genes are important in chemical carcinogenesis, but as the methodology for studying other genes improves, their roles will be seen in perspective.

Publication types

  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Carcinogens / toxicity*
  • Codon / chemistry
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / genetics*
  • Genes, Tumor Suppressor / physiology
  • Genes, ras / genetics
  • Humans
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / genetics
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / genetics
  • Mice
  • Molecular Sequence Data
  • Mutation / drug effects
  • Mutation / genetics
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / genetics*
  • Oncogenes / genetics*
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / genetics

Substances

  • Carcinogens
  • Codon