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Experimental chemical carcinogenesis in the stomach and colon.

Abstract
Experimental chemical carcinogenesis in the digestive tract is reviewed, mainly on the basis of information obtained in the laboratories of the National Cancer Center Research Institute. It is generally accepted that cancer is the outcome of DNA damage, resulting in mutation, loss, amplification and recombination of genes. Gastric cancer is no exception. It was shown very early that cancer of the glandular stomach can be produced in rats by administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a widely used mutagen. However, this depends on the genotype. Whereas the ACI rat is susceptible to MNNG, the Buffalo rat is resistant and this is a dominantly inherited trait. Genes responsible for the sensitivity to gastric cancer induction are at present under investigation by linkage analysis of rat genome markers. With regard to cancer in humans, our finding that cooked proteinaceous foods can give rise to a series of heterocyclic amines (HCAs) is of major significance. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the most abundant, causes colon cancers in male rats, whereas in females it induces breast cancers. The colon cancers induced by PhIP feature a deletion of G as represented by 5-GGGA-3-->5-GGA-3 in the Apc gene, resulting in a truncated Apc molecule. Microsatellite mutations have also been found in PhIP-induced colon tumors, as in human hereditary non-polyposis colorectal cancer cases. Similarly to the case of gastric cancer production by MNNG, there is a genetic component and F344 rats are more susceptible to PhIP colon carcinogenesis than the ACI/N strain and the gene responsible is being sought. Since carcinogenesis proceeds with accumulation of genetic alteration, often involving genomic instability, exposure to any kind of carcinogenic substances, either xeno- or autobiotics, needs to be reduced as far as possible, taking account of inconvenience at the individual and socio-economical levels.
AuthorsT Sugimura, M Terada
JournalJapanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 28 Issue 3 Pg. 163-7 (Mar 1998) ISSN: 0368-2811 [Print] England
PMID9614437 (Publication Type: Journal Article, Review)
Chemical References
  • Carrier Proteins
  • DNA, Neoplasm
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • PDCL protein, human
  • Pdcl protein, rat
  • Receptors, Aryl Hydrocarbon
  • Methylnitronitrosoguanidine
Topics
  • Adenomatous Polyposis Coli (genetics)
  • Animals
  • Carrier Proteins (genetics)
  • Colonic Neoplasms (chemically induced, genetics)
  • DNA, Neoplasm (physiology)
  • Gene Deletion
  • Genes, APC
  • Humans
  • Male
  • Methylnitronitrosoguanidine
  • Molecular Chaperones
  • Nerve Tissue Proteins (genetics)
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred BUF
  • Rats, Inbred F344
  • Rats, Wistar
  • Receptors, Aryl Hydrocarbon
  • Stomach Neoplasms (chemically induced, genetics)

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