title: Enhancement of the morphological transformation of Syrian hamster embryo (SHE) cells by reducing incubation time of the target cells.
abstract: Syrian hamster embryo (SHE) cell transformation has been used for many years to study chemical carcinogenesis in vitro. It has been shown that this assay is probably the most predictive short-term test system for identifying rodent carcinogens. Although most of the operational difficulties encountered in the early stage of application of this assay have been overcome by culturing the SHE cells under slightly acidic conditions (pH 6.7), a relatively low level of induction of morphological transformation (MT) by known carcinogens still occurs for many cell isolates. In order to improve the response of this assay system to known carcinogens, the effect of incubation time of target SHE cells on the frequency of morphological transformation induced by benzo(a)pyrene (BaP) was investigated. It was shown that the morphological transformation frequency induced by BaP increased significantly (1.4-2.5-fold) when the incubation time of target cells was reduced from the usual 24h to less than 6h prior to seeding onto feeder layers. This improvement in sensitivity was consistent for different cell isolates. In addition, the enhanced response appeared to be a property of carcinogens because treatment with two non-carcinogens, l-ascorbic acid and 4-nitro-o-phenylenediamine, did not induce significant increases in the transformation frequency under the shortened incubation period for target cells. These results suggest that the response of the SHE cell transformation assay may be improved by optimizing the incubation time of the target SHE cells. In addition, the results of the present study provide further evidence to support the idea that morphological transformation of SHE cells results from a block of cellular differentiation of stem or stem-like cells.
authors.affiliation: Genetic and Molecular Toxicology, Covance Laboratories Inc., 9200 Leesburg Pike, Vienna, VA 22182, USA. haizhou.zhang@covance.com
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: H D
authors.initials: HD
authors.lastname: Borman
authors.forename: B C
authors.initials: BC
authors.lastname: Myhr
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence; D006224:Cricetinae; D008647:Mesocricetus; D010655:Phenylenediamines; D013997:Time Factors
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D010655:Phenylenediamines; D001564:Benzo(a)pyrene; C012277:1,2-diamino-4-nitrobenzene; D001205:Ascorbic Acid