title: High-throughput screening system for identifying phototoxic potential of drug candidates based on derivatives of reactive oxygen metabolites.
abstract: OBJECTIVE
  The present study aimed to develop a high-throughput screening strategy for predicting the phototoxic potential of pharmaceutical substances, using a derivatives-of-reactive-oxygen-metabolites (D-ROM) assay.
  
  
  METHODS
  The assay conditions of the D-ROM assay were optimized with a focus on screening run time, sensitivity, solvent system, and reproducibility. The phototoxic potentials of 25 model compounds were assessed by the D-ROM assay, as well as by other screening systems for comparison, including the reactive oxygen species (ROS) assay, the DNA-photocleavage assay, and the 3T3 neutral red uptake phototoxicity test (3T3 NRU PT).
  
  
  RESULTS
  Some phototoxic drugs tended to yield D-ROM when exposed to simulated sunlight (250 W/m(2)), whereas D-ROM generation was negligible for non-phototoxic chemicals. Compared with the ROS assay, the assay procedure for the D-ROM assay was highly simplified with a marked reduction in screening run time. Comparative experiments also demonstrated that D-ROM data were related to the outcomes of the DNA-photocleavage assay and the 3T3 NRU PT, with prediction accuracies of 76 and 72%, respectively.
  
  
  CONCLUSIONS
  The D-ROM assay has potential for identifying the phototoxic potential of a large number of new drugs as a 1st screening system in the early stages of drug discovery.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.forename: Masanori
authors.initials: M
authors.lastname: Ochi
authors.forename: Graham
authors.initials: G
authors.lastname: Gandy
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.forename: Naoko
authors.initials: N
authors.lastname: Igarashi
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D007202:Indicators and Reagents / Q000737:chemistry; D008027:Light; D051379:Mice; D018625:Microscopy, Atomic Force; D009499:Neutral Red / Q000737:chemistry; D010545:Peroxides / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D013053:Spectrophotometry
chemical_list: D007202:Indicators and Reagents; D010545:Peroxides; D017382:Reactive Oxygen Species; D009499:Neutral Red; C049375:perhydroxyl radical; D004247:DNA