1 research outputs found
Characterization and Biological Potency of Mono- to Tetra-Halogenated Carbazoles
This
paper deals with the characterization and aryl hydrocarbon
receptor (AhR) agonist activities of a series of chlorinated, brominated,
and mixed bromo/chlorocarbazoles, some of which have been identified
in various environmental samples. Attention is directed here to the
possibility that halogenated carbazoles may currently be emitted into
the environment as a result of the production of carbazole-containing
polymers present in a wide variety of electronic devices. We have
found that any carbazole that is not substituted in the 1,3,6,8 positions
may be lost during cleanup of environmental extracts if a multilayer
column is utilized, as is common practice for polychlorinated dibenzo-<i>p</i>-dioxin (dioxin) and related compounds. In the present
study, <sup>1</sup>H NMR spectral shift data for 11 relevant halogenated
carbazoles are reported, along with their gas chromatographic separation
and analysis by mass spectrometry. These characterization data allow
for confident structural assignments and the derivation of possible
correlations between structure and toxicity based on the halogenation
patterns of the isomers investigated. Some halogenated carbazoles
exhibit characteristics of persistent organic pollutants and their
potential dioxin-like activity was further investigated. The structure-dependent
induction of CYP1A1 and CYP1B1 gene expression in Ah-responsive MDA-MB-468
breast cancer cells by these carbazoles was similar to that observed
for other dioxin-like compounds, and the magnitude of the fold induction
responses for the most active halogenated carbazoles was similar to
that observed for 2,3,7,8-tetrachlorodibenzo<i>-p-</i>dioxin
(TCDD). 2,3,6,7-Tetrachlorocarbazole was one of the most active halogenated
carbazoles and, like TCDD, contains 4 lateral substituents; however,
the estimated relative effect potency for this compound (compared
to TCDD) was 0.0001 and 0.0032, based on induction of CYP1A1 and CYP1B1
mRNA, respectively