Abstract |
Aberrant crypt foci (ACF) are putative preneoplastic lesions that develop after treatment of animals with colon carcinogens, including cooked-meat heterocyclic amines such as 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). Male F344 rats given IQ by gavage on alternating days for 2 wk (130 mg/kg body weight) and killed 12 wk after the final carcinogen dose had an average of 4.4 ACF/colon and an average of 3.2 crypts/focus. The DNA from these ACF was amplified by the polymerase chain reaction and analyzed by 3'-primer mismatch and direct sequencing methods for mutations in the Ki-ras proto-oncogene. Of the 37 IQ-induced ACF screened, three contained a GGT--> GAT mutation in codon 12 and one contained a GGC-->GCC mutation in codon 13. The approximately 11% frequency of mutation in IQ-induced ACF is within the range of previous ACF studies of azoxymethane, which reported a 7-37% incidence of Ki-ras mutation. These findings suggest that for both compounds, ras mutations occur during early stages of colorectal tumorigenesis. However, while ras mutations can be detected with increasing frequency in azoxymethane-induced adenomas and carcinomas, they are reportedly absent in IQ-induced colon tumors. Thus, for IQ and related compounds additional factors (possibly increased cell proliferation) may be important in the later stages of colorectal tumorigenesis.
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Authors | N Tachino, R Hayashi, C Liew, G Bailey, R Dashwood |
Journal | Molecular carcinogenesis
(Mol Carcinog)
Vol. 12
Issue 4
Pg. 187-92
(Apr 1995)
ISSN: 0899-1987 [Print] United States |
PMID | 7727039
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carcinogens
- DNA Primers
- Quinolines
- 2-amino-3-methylimidazo(4,5-f)quinoline
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Topics |
- Animals
- Base Sequence
- Carcinogens
(toxicity)
- Cell Transformation, Neoplastic
- Colon
(drug effects, metabolism, pathology)
- DNA Primers
- Genes, ras
- Male
- Molecular Sequence Data
- Mutagenesis
- Point Mutation
- Polymerase Chain Reaction
- Quinolines
(toxicity)
- Rats
- Rats, Inbred F344
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