title: Preincision complex-I from the excision nuclease reaction among cochlear spiral limbus and outer hair cells.
abstract: The excision nuclease reaction defends the genome from endogenous and exogenous mutagens. The rate-limiting step in the reaction is facilitated by preincision complex-1 (PIC-1). PIC-1 is maintained by xeroderma pigmentosum A and C (XPA and XPC) through protein-protein interactions and DNA binding. XPA and XPC exhibit high-affinity for DNA adducts from the anticancer molecule, cisplatin. Systemic cisplatin treatment results in ubiquitous DNA adducts in the cochlea. Cochleae harvested from patients treated with cisplatin reveal dead outer hair cells among normal spiral limbus cells. Such discrepancy, suggest differences in genome defense repertoire among cochlear cells. The purpose of this study was to use cisplatin as a stimulus to examine XPA and XPC immunoreactivity among outer hair cells and spiral limbus cells. Fischer344 rats were treated with either one or two cycles of cisplatin, where each cycle lasted four days and separated by a 10 day rest period. Cochleae were harvested after each treatment cycle and four days after the second treatment cycle then processed for immunohistochemistry. Unlike spiral limbus cells, outer hair cells failed to acclimate to the cisplatin treatment cycles by regulating XPA and XPC immunoreactivity. These results imply that outer hair cells may have a limited capacity to mobilize PIC-I beyond basal demand.
authors.affiliation: Department of Communication Science and Disorders, University of Pittsburgh, Forbes Tower 4033, Pittsburgh, PA 15260, USA. owg@duke.edu
authors.forename: O'neil W
authors.initials: OW
authors.lastname: Guthrie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D003051:Cochlea / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D051760:Xeroderma Pigmentosum Group A Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D046911:Macromolecular Substances; C534808:XPC protein, rat; D051760:Xeroderma Pigmentosum Group A Protein; D002945:Cisplatin