EARLY DETECTION OF CANCER-ASSOCIATED GENE ALTERATIONS IN DNA ISOLATED FROM RAT FECES DURING INTESTINAL TUMOR-INDUCTION WITH 1,2-DIMETHYLHYDRAZINE

  • Authors:
    • A LOKTIONOV
    • IK ONEILL
  • View Affiliations

  • Published online on: February 1, 1995     https://doi.org/10.3892/ijo.6.2.437
  • Pages: 437-445
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Abstract

A highly sensitive mutation detection method was applied to reveal tarry K-ras alterations in exfoliated intestinal epithelium of Fischer-344 rats during the course of 1,2-dimethylhydrazine (DMH)-induced carcinogenesis. Ten weekly s.c. injections of DMH (50 mg/kg) in combination with consumption of a low-fiber diet resulted in 100% incidence of intestinal tumors at 20 weeks after initial DMH injection. Analysis of DNA extracted from fresh fecal samples obtained individually showed that proportion of codon 12 K-ras oncogene mutant alleles (G-->A transition at the second position of codon 12) was increased in some rats at 4 weeks and clearly in all rats at 8 weeks after initial DMH injection, i.e. much earlier than the first tumors appeared (14 weeks). A gradual increase of mutant K-ras fraction in DNA samples extracted from feces led to an extremely high level of the mutant reaching 10% of the oncogene alleles at the end of the experiment (20 weeks). K- and H-ras oncogene and p53 tumor suppressor gene mutations were analyzed in the resulting colon and duodenal tumors. 14 of 17 colon tumors had K-P as mutations (11 - G-->A transition at codon 12 second base; 3 - G-->A transition at codon 13 second base). G-->A transitions at codon 12 first base of H-ras were detected in 3 colon tumors. All 5 duodenal tumors induced in the experiment had G-->A transition at codon 12 second base of K-ras. 3 of these tumors also had H-ras mutations. No mutation was detected within exons 4-7 of p53 gene indicating that p53 alterations may not be involved in the rapid development of tumors induced by high doses of DMH. Our observations suggest that detection of K-ras mutations in stool samples are predictive of later tumor development from a very early stage.

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February 1995
Volume 6 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
LOKTIONOV, A., & LOKTIONOV, A. (1995). EARLY DETECTION OF CANCER-ASSOCIATED GENE ALTERATIONS IN DNA ISOLATED FROM RAT FECES DURING INTESTINAL TUMOR-INDUCTION WITH 1,2-DIMETHYLHYDRAZINE. International Journal of Oncology, 6, 437-445. https://doi.org/10.3892/ijo.6.2.437
MLA
LOKTIONOV, A., ONEILL, I."EARLY DETECTION OF CANCER-ASSOCIATED GENE ALTERATIONS IN DNA ISOLATED FROM RAT FECES DURING INTESTINAL TUMOR-INDUCTION WITH 1,2-DIMETHYLHYDRAZINE". International Journal of Oncology 6.2 (1995): 437-445.
Chicago
LOKTIONOV, A., ONEILL, I."EARLY DETECTION OF CANCER-ASSOCIATED GENE ALTERATIONS IN DNA ISOLATED FROM RAT FECES DURING INTESTINAL TUMOR-INDUCTION WITH 1,2-DIMETHYLHYDRAZINE". International Journal of Oncology 6, no. 2 (1995): 437-445. https://doi.org/10.3892/ijo.6.2.437