Unequal recombination events between Alu elements contribute to a significant portion of human genome instabilities associated with cancer and birth defects. There are over 50 independent examples of Alu/Alu recombination events causing different human diseases. Previous studies have shown that various mutagenic compounds contribute to increased recombination rates between randomly repeated sequences. These assays have demonstrated that recombination environmental pollutants often have different influences on small mutations versus recombination. We hypothesize that mutagens will also contribute to the more recombination between dispersed Alu elements, although the stimulation by different mutagens may not be identical between these two different types of recombinant. Thus, we have designed a reported system that will be introduced into tissue culture cells and transgenic mice to allow the direct measurement of Alu/Alu recombination rates. We believe that this assay will be more representative of typical recombination events occurring in the human genome than previous assays. The Alu/Alu recombination assay will be utilized to test for increases in recombination rate upon exposure to a broad range of mutagens. Particular attention will be paid to the aryl hydrocarbons because they represent such a ubiquitous and stable class of pollutants. In particular, studies of benzo[a]pyrene versus. various halogenated aromatic hydrocarbons will be carried out to determine whether there are differences in recombination potential between the more metabolizable hydrocarbons versus no-.metabolizable ones. In addition, studies to determine the role of the aryl hydrocarbon receptor in any recombination stimulation will be carried out.
| Cohn, William B; Jones, Richard A; Valverde, Roldan A et al. (2010) Molecular cloning and regulation of mRNA expression of the thyrotropin ? and glycoprotein hormone ? subunits in red drum, Sciaenops ocellatus. Fish Physiol Biochem 36:1277-90 |
| Kale, Shubha P; Carmichael, Mary C; Harris, Kelley et al. (2006) The L1 retrotranspositional stimulation by particulate and soluble cadmium exposure is independent of the generation of DNA breaks. Int J Environ Res Public Health 3:121-8 |
| Gonzalez-Villalobos, Romer; Klassen, R Bryan; Allen, Patricia L et al. (2006) Megalin binds and internalizes angiotensin-(1-7). Am J Physiol Renal Physiol 290:F1270-5 |
| Klassen, R Bryan S; Allen, Patricia L; Batuman, Vecihi et al. (2005) Light chains are a ligand for megalin. J Appl Physiol 98:257-63 |
| Kale, Shubha P; Moore, Lakisha; Deininger, Prescott L et al. (2005) Heavy metals stimulate human LINE-1 retrotransposition. Int J Environ Res Public Health 2:14-23 |
| Gonzalez-Villalobos, Romer; Klassen, R Bryan; Allen, Patricia L et al. (2005) Megalin binds and internalizes angiotensin II. Am J Physiol Renal Physiol 288:F420-7 |
| El-Sawy, Mohammed; Kale, Shubha P; Dugan, Christine et al. (2005) Nickel stimulates L1 retrotransposition by a post-transcriptional mechanism. J Mol Biol 354:246-57 |
| D'Elia, Riccardo; Allen, Patricia L; Johanson, Kelly et al. (2005) Homozygous diploid deletion strains of Saccharomyces cerevisiae that determine lag phase and dehydration tolerance. Appl Microbiol Biotechnol 67:816-26 |
| Roy-Engel, A M; El-Sawy, M; Farooq, L et al. (2005) Human retroelements may introduce intragenic polyadenylation signals. Cytogenet Genome Res 110:365-71 |
| Klassen, R Bryan; Crenshaw, Kimberly; Kozyraki, Renata et al. (2004) Megalin mediates renal uptake of heavy metal metallothionein complexes. Am J Physiol Renal Physiol 287:F393-403 |
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