Phenotypic anchoring of arsenic and cadmium toxicity in three hepatic-related cell systems reveals compound- and cell-specific selective up-regulation of stress protein expression: Implications for fingerprint profiling of cytotoxicity.

Gottschalg, E., Moore, N.E., Ryan, A.K., Travis, L.C., Waller, R.C., Pratt, S., Atmaca, M., Kind, C.N. and Fry, J.R.

Chemico-Biological Interactions, 161, 251-261 (2006).

Exposure of cells to toxic chemicals is known to up-regulate the expression of a number of stress proteins (SPs), including metallothionein (MT) and members of the heat shock protein (HSP) family, and this response may allow the development of a fingerprint profile to identify mechanisms of toxicity in an in vitro toxicology setting. To test this hypothesis, three hepatic-derived cell culture systems (rat hepatoma FGC4 cell line, rat hepatocytes, human hepatoma HepG2 cell line) were exposed to cadmium (as CdCl₂) and arsenic (as NaAsO₂), two compounds believed to exert their toxicity through an oxidative stress mechanism, under conditions of phenotypic anchoring defined as minimal and mild toxicity (approximately 5 and 25% reduction in neutral red uptake, respectively). The expression of six SPs – MT, HSP25/27, HSP40, HSP60, HSP70, and HSP90 – was then determined by ELISA. Expression of four of these SPs – MT, HSP25/27, HSP40 and HSP70 – was up-regulated in at least one experimental condition. However, the patterns of expression of these four SPs varied across the experimental con