title: Evaluation of differential representative values between Chinese hamster cells and human lymphocytes in mitomycin C-induced cytogenetic assays and caspase-3 activity.
abstract: Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.
authors.affiliation: 1Department of Pharmacology, School of Medicine, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Pei-Hu
authors.initials: PH
authors.lastname: Liao
authors.forename: Ruey-Hseng
authors.initials: RH
authors.lastname: Lin
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Yang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Li
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Kuan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002460:Cell Line; D002869:Chromosome Aberrations / Q000139:chemically induced; D006224:Cricetinae; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D020732:Cytogenetic Analysis / Q000379:methods / Q000592:standards; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D016685:Mitomycin / Q000633:toxicity*; D009152:Mutagenicity Tests; D009842:Oligopeptides / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D016685:Mitomycin; D053148:Caspase 3