title: Expression of delayed cell death (DCD) in the progeny of fish cells surviving 2,4-dichloroaniline (2,4-DCA) exposure.
abstract: Interest in and concern for the quality of the environment has prompted a great deal of research into methods of measuring and assessing changes in it. One problem of major interest is that of increasing amounts of mutagenic/carcinogenic chemicals generated and released into marine and freshwater ecosystems. Numerous techniques involving whole animals and cell culture for these genotoxic changes have been devised to assay specific chemicals. Little has been done to determine the effects of potential genotoxicants on aquatic organisms. The purpose of this study was to investigate if 2,4-Dichloroaniline (2,4-DCA) (CASRN: 554-00-7), induced delayed cell death (DCD) or delayed reproductive cell death a.k.a. as lethal mutations in a teleost cell line, CHSE-214. Delayed expression of cell death in the progeny of cells, which survived a toxic insult, was first shown for ionizing radiation and is one of the signs of induced genomic instability. The survival of cells initially treated with 2,4-DCA and the survival of their progeny were determined. When cells are exposed to a toxic insult, the component cells of a normal appearing survivor colony or clone were commonly thought to have proliferative capacity equivalent to that of the untreated cells. In this study, however, it was found that CHSE-214 cells surviving 2,4-DCA exposure carried heritable lethal defects, which came to light only after numerous apparently successful divisions, in the form of plating efficiencies, which were reduced below those of the untreated, control cells. DCD expression did not appear to be dose-dependent with poor cell survival occurring at the lower end of 2,4-DCA exposure and remained constant until recovering to something like 60% of the controls. A study of the CHSE-214 kinetics post-exposure showed that the apparent reduced growth rate of the cells was due to reduced numbers of reproductively viable cells in the population. Results showed that the expression of DCD occurred persistently post-treatment and was relatively independent of dose once a threshold level of 40 microM (Fig. 1) had been reached.
authors.affiliation: Department of Zoology and Animal Ecology, Environmental Research Institute, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland. m.kilemade@ucc.ie
authors.forename: Michael
authors.initials: M
authors.lastname: Kilemade
authors.forename: Carmel
authors.initials: C
authors.lastname: Mothersill
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay / Q000379:methods; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D012474:Salmon; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000814:Aniline Compounds; D009153:Mutagens; D014874:Water Pollutants, Chemical; C054619:2,4-dichloroaniline