UV radiation induces delayed hyperrecombination associated with hypermutation in human cells
Stephen T Durant1, Kimberly S Paffett, Meena Shrivastav
1Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Molecular and Cellular Biology
|August 2, 2006
Summary
Ultraviolet-C radiation causes delayed hyperrecombination in human cells, a phenomenon linked to increased oxidative stress. This delayed genomic instability may contribute to skin cancer development.
Area of Science:
- Genetics
- Molecular Biology
- Radiation Biology
Background:
- Ionizing radiation is known to induce delayed genomic instability in human cells.
- This instability manifests as chromosomal abnormalities and hyperrecombination.
- The effects of ultraviolet (UV) radiation on delayed genome instability are less understood.
Purpose of the Study:
- To investigate delayed genome instability in human cells exposed to UV radiation.
- To examine the induction of delayed hyperrecombination (DHR) by UV-C and UV-B radiation.
- To explore the relationship between UV-induced DHR and hypermutation.
Main Methods:
- Assessed homologous recombination-mediated reactivation of a green fluorescent protein (GFP) gene in p53-proficient human cells.
- Exposed cells to specific doses of UV-C and UV-B radiation.
- Analyzed hypoxanthine phosphoribosyltransferase (HPRT) mutation frequencies and spectra in surviving cell strains.
Main Results:
- UV-C radiation (5 J/m2) induced an approximately 5-fold enhancement of DHR, observed as mixed GFP+/- colonies.
- UV-B radiation did not induce DHR at equitoxic or higher doses.
- UV-induced DHR strains exhibited approximately 5-fold higher HPRT mutation frequencies, characterized by small, compound mutations, suggesting a common origin with oxidative stress.
Conclusions:
- UV-C radiation induces delayed hyperrecombination (DHR) in human cells.
- UV-induced DHR and hypermutation likely stem from a common source: increased oxidative stress.
- These distinct forms of delayed genome instability may cooperatively contribute to skin cancer initiation and progression.
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