INDUCED GENE-TRANSCRIPTION - IMPLICATIONS FOR BIOMARKERS

Numerous xenobiotics regulate cellular functions by altering transcrip tion of target genes, Use of sensitive and specific biomarkers based o n gene transcript levels may help clarify the shape of the dose-respon se curve in the low-dose region associated with human exposures to env ironmental concentrations of chemicals. We have quantified gene transc ription induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in both animal models and humans with the use of Northern analysis and PCR-based meth ods, In addition, we describe a rapid and sensitive in vitro assay tha t we have used to screen chemicals and biological samples for their ab ility to alter gene transcription. Whereas some of the endpoints in ou r studies such as cytochrome P-450 1A1 are predictive indicators of ex posure and dose, other gene responses such as growth factors are more complex and represent a critical event, progression, or adaptation to a pathological alteration. In conclusion, measurement of toxicant-indu ced gene transcription will contribute to the usefulness of biomarkers in addressing issues of human health and environmentally induced dise ase.