Defining a No Observable Transcriptional Effect Level (NOTEL) for low dose N-OH-PhIP exposures in human BEAS-2B bronchioepithelial cells

The estimation of acceptable exposure levels for genotoxicants is accomplished by defining thresholds from apical endpoints, or by modeling points of departure from data that are acquired from high dose experiments, followed by linear extrapolation of the response through zero. We recently proposed that low dose exposure-induced transcriptional changes that can be linked to mechanisms of pathogenesis could provide a more sensitive alternative for defining thresholds for biological responses. In the present study, we used gene expression profiling data to determine an empirical transcriptional dose response threshold for the food and tobacco smoke borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (PhIP) in human BEAS-2B bronchial epithelial cells exposed to concentrations of N-hydroxylated PhIP ranging from 1 x 10-6 to 5 x 10-10 M.

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