title: Detection of chemical-induced unscheduled DNA synthesis in cultures of normal adult human keratinocytes.
abstract: Human keratinocytes are the most appropriate target cells to employ in an in vitro model to study the potential ability of a chemical to react with the genome of human skin cells. The resulting damage to DNA may be a key initiating factor in the subsequent development of squamous epithelial carcinoma, which is a common form of cancer in humans. Keratinocytes were routinely established from adult human skin samples and maintained in culture for at least three passages. Genotoxic damage was assessed by a quantitative autoradiographic technique which enables detection of unscheduled DNA synthesis without prior treatment of the cultures with agents, such as hydroxyurea, to suppress S-phase synthesis. Tertiary cultures from two individuals were exposed to the experimental carcinogens, methyl methane sulphonate (direct-acting genotoxin) and benzo[a]pyrene (requiring metabolic activation). Both chemicals induced unscheduled DNA synthesis in human keratinocytes. This study indicates that human keratinocyte cultures are a suitable model for the detection of genotoxic potential in human epidermis.
authors: Robens Institute of Health and Safety, University of Surrey, Guildford, Surrey GU2 5XH, UK.
authors: J N
authors: JN
authors: Lawrence
authors: D J
authors: DJ
authors: Benford