Bromophenols, both present in marine organisms and in industrial flame retardants, disturb cellular Ca2+ signaling in neuroendocrine cells (PC12)

Bromophenols are present in polychaetes as well as in algae in marine environments including the North Sea. They are thought to cause the typical sea-like taste and flavour. The ecological function of brominated Phenols is not clear yet, but they may play a role in chemical defence and deterrence [Kicklighter, C.E., Kubaneck, J., Hay, M.E., 2004. Do brominated natural products defend marine worms from consumers? Some do, most don't. Limnol. Oceanogr. 49, 430-441]. Some brominated Phenols are commercially used as industrial flame retardants as, e.g., 2,4,6-tribromophenol and are suspected to disrupt the humoral system by showing thyroid hormone-like activity [Legler, I., Brouwer, A., 2003. Are brominated flame retardants endocrine disruptors? Environ. Int. 29, 879-885]. In this study 2-bromophenol (2-BP), 4-bromophenol (4-BP), 2,4-dibromophenol (2,4-DBP), 2,6-dibromophenol (2,6-DBP) and 2,4,6-tribromophenol (2,4,6-TBP), all of which are present in marine organisms, were tested. Especially 2,4-DBP and 2,4,6-TBP showed a significant effect on the Ca2+ homeostasis in endocrine cells (PC 12). The reduction of depolarization induced Ca2+ elevations by 2,4-DBP and 2,4,6-TBP and the increase of intracellular Ca2+ by both substances, partly released from intracellular stores, may suggest a link to the disrupting effect of endocrine systems by brominated Phenols. 2,4-DBP was the most potent substance we tested in respect to inhibition of voltage dependent Ca2+ currents as revealed in whole cell patch clamp experiments. Brominated Phenols disturb cellular Ca2+ signaling with differential efficacy, depending on the number and position of bromine.