title: Prostaglandin E(2) release in keratinocyte cultures following exposure to various tumour promoters.
abstract: The interaction of tumour promoters with the target cell type (keratinocyte) may be an essential feature of their promoting activity and their ability to initiate an inflammatory response. The role of prostaglandin E(2) (PGE(2)), particularly in the keratinocyte, remains largely unknown, but it is closely associated with inflammation and regenerative epidermal hyperplasia, which appear critical for tumour promotion. Rat keratinocytes derived from sublingual mucosa represent a suitable model to investigate the ability of several irritants, of varying tumour-promoting potency, to stimulate PGE(2) release. Cytotoxicity was evaluated by the neutral red uptake assay and a concentration that reduced cell viability to 50% of control was selected as a maximum concentration for subsequent measurement of PGE(2) release. Phorbol-12-myristate-13-acetate, ionophore A23187 and mezerein stimulated PGE(2) release at non-toxic concentrations. Anthralin, benzoyl peroxide, sodium dodecyl sulfate and acetic acid did not stimulate PGE(2) at non-toxic concentrations, but release was associated with a toxic response. Epidermal growth factor and phospholipase C, which are closely associated with intracellular signalling systems that modulate keratinocyte proliferation and differentiation, also stimulated PGE(2) release. Epidermal growth factor elicited PGE(2) release at a concentration reported to be mitogenic in keratinocyte cultures. The stimulation of PGE(2) release in the absence of a toxic response by PMA, mezerein and ionophore A23187 may be indicative of a direct interaction of the chemicals with intracellular pathways involved in regulation of keratinocyte differentiation and proliferation. This interaction may also reflect the ability of such chemicals to initiate an inflammatory response. Measurement of PGE(2) release may be useful to investigate further the mechanism of action of tumour promoters in the target cell type. In contrast, other tumour promoters did not stimulate release at non-toxic concentrations, which implies that their ability to initiate an inflammatory response and possibly their promoting activity is associated with the induction of a toxic response in the target cell population.
authors.affiliation: Robens Institute of Health and Safety, University of Surrey, Guildford, Surrey GU2 5XH, UK.
authors.forename: J N
authors.initials: JN
authors.lastname: Lawrence
authors.forename: D J
authors.initials: DJ
authors.lastname: Benford