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Carcinogens induce intrachromosomal recombination in human cells
J Aubrecht1, R Rugo, R H Schiestl
1Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
Carcinogenesis
|November 1, 1995
Summary
Environmental carcinogens linked to cancer may not be detected by the Ames test. This study shows carcinogen exposure induces intrachromosomal recombination and deletions in human cells, suggesting a role in cancer development.
Area of Science:
- Environmental Health
- Molecular Biology
- Cancer Research
Background:
- Environmental carcinogens are a significant factor in cancer development.
- The Ames (Salmonella) test is a common short-term assay for carcinogenicity, but it fails to detect approximately 50% of known carcinogens.
- Limitations of current short-term assays necessitate the development of alternative methods to identify potential carcinogens.
Purpose of the Study:
- To investigate the effect of carcinogen exposure on intrachromosomal recombination in a human cell line.
- To determine if both Ames test-positive and Ames test-negative carcinogens induce recombination and deletion events.
Main Methods:
- Utilized a human cell line engineered to detect intrachromosomal recombination.
- Exposed cells to a panel of known carcinogens, including those positive and negative in the Ames test.
- Quantified deletion events resulting from recombination within the hprt gene.
Main Results:
- Carcinogen exposure induced intrachromosomal recombination events, leading to deletions.
- Deletion events were observed following exposure to Ames test-positive carcinogens (UV, gamma-rays, methyl methanesulfonate).
- Crucially, similar deletion events were also induced by Ames test-negative carcinogens (Aroclor 1221, benzene, thiourea).
Conclusions:
- Intrachromosomal recombination and subsequent deletions are induced by a broad range of environmental carcinogens, irrespective of their mutagenicity in the Ames test.
- These findings suggest that recombination and deletion mechanisms may play a significant role in the initiation and progression of carcinogenesis.
- This study highlights the potential of using recombination assays in human cells as a complementary approach for detecting environmental carcinogens.