232
of interference with either thyroid hormone metabolism [92–94] or thyroid hormone transport [95–97].
Some BFRs can act as hormones, estrogen agonists, or antagonists, and can lead
to serious consequences such as reproductive disorders and carcinogenesis. To
investigate antagonistic activity of BFRs to estrogen, an in vitro receptor-mediated
reporter gene assay employing human breast cancer cells was exploited. In this
assay, an estrogen receptor-mediated luciferase reporter genome complex, which
was decorated with three estrogen response characters, was presented and incorporated in the genetic material of the T47Dcells [98]. Introduction of xenobiotic estrogens leads to diffusion of chemical entities across the plasma membrane, attachment
to the endogenous estrogen receptors, stimulation of the receptor, and ultimately,
annexing to the ligand-receptor structure to estrogen response elements located in
the promoter site of the luciferase gene. Thus, luciferase protein is tempted and
conveniently measured by rupturing or lysing the cells, adding luciferin substrate,
and quantifying light photon generation. In research studies with BFR exposure,
brominated diphenyl ether-47 exhibited weak estrogenic activity compared with
that of estradiol. Some polybrominated bisphenol resembling structures, such as
monobromobisphenol A and dibromobisphenol A, demonstrated greater estrogenic
activity than those of brominated diphenyl ethers. In other investigations, polybrominated biphenol tetrabromobisphenol A also demonstrated attachment to estrogen
receptors, and encouraged proliferation of estrogen-dependent MCF-7 cells [99,
100] and MtT/E2 cells [101]. PBDPEs also exhibit antagonistic activity to estrogen
when investigated in vitro at micromolar titers in conjunction with estradiol, including brominated diphenyl ether-153, brominated diphenyl ether-166, and brominated
diphenyl ether-190 [97]. However, Villeneuve and co-workers could not find any
compelling evidence of estrogenic potency of brominated diphenyl ether-47, brominated diphenyl ether-100, and brominated diphenyl ether-75 [102]. This incongruity
might be attributed to estrogens that originate in human breast cancer cells
(ER-CALUX) compared with the MVLN reporter gene assay [98]. Only a few
research investigations on exclusive estrogenic properties of brominated flame
retardants in vivo are available. Irrespective of its in vitro estrogenic effects, investigations involving in ovo introduction of tetrabromobisphenol A have demonstrated
no estrogenic activity in birds, such as quail and chicken embryos [103]. This apparent deficiency in estrogenic characteristics might be owing to the prompt biotransformation of tetrabromobisphenol A in vivo, as revealed in both rats [104] and
quail [105].
Conclusions
Fire has played a major role in shaping human society and is an essential component
of many religions and ancient mythologies. Stopping or retarding unwanted fire has
always been desired; this coupled with advances of chemical know-how, we have a
variety of chemical substances for this specific task, known as fire retardants. With
T. Hussain et al.
of interference with either thyroid hormone metabolism [92–94] or thyroid hormone transport [95–97].
Some BFRs can act as hormones, estrogen agonists, or antagonists, and can lead
to serious consequences such as reproductive disorders and carcinogenesis. To
investigate antagonistic activity of BFRs to estrogen, an in vitro receptor-mediated
reporter gene assay employing human breast cancer cells was exploited. In this
assay, an estrogen receptor-mediated luciferase reporter genome complex, which
was decorated with three estrogen response characters, was presented and incorporated in the genetic material of the T47Dcells [98]. Introduction of xenobiotic estrogens leads to diffusion of chemical entities across the plasma membrane, attachment
to the endogenous estrogen receptors, stimulation of the receptor, and ultimately,
annexing to the ligand-receptor structure to estrogen response elements located in
the promoter site of the luciferase gene. Thus, luciferase protein is tempted and
conveniently measured by rupturing or lysing the cells, adding luciferin substrate,
and quantifying light photon generation. In research studies with BFR exposure,
brominated diphenyl ether-47 exhibited weak estrogenic activity compared with
that of estradiol. Some polybrominated bisphenol resembling structures, such as
monobromobisphenol A and dibromobisphenol A, demonstrated greater estrogenic
activity than those of brominated diphenyl ethers. In other investigations, polybrominated biphenol tetrabromobisphenol A also demonstrated attachment to estrogen
receptors, and encouraged proliferation of estrogen-dependent MCF-7 cells [99,
100] and MtT/E2 cells [101]. PBDPEs also exhibit antagonistic activity to estrogen
when investigated in vitro at micromolar titers in conjunction with estradiol, including brominated diphenyl ether-153, brominated diphenyl ether-166, and brominated
diphenyl ether-190 [97]. However, Villeneuve and co-workers could not find any
compelling evidence of estrogenic potency of brominated diphenyl ether-47, brominated diphenyl ether-100, and brominated diphenyl ether-75 [102]. This incongruity
might be attributed to estrogens that originate in human breast cancer cells
(ER-CALUX) compared with the MVLN reporter gene assay [98]. Only a few
research investigations on exclusive estrogenic properties of brominated flame
retardants in vivo are available. Irrespective of its in vitro estrogenic effects, investigations involving in ovo introduction of tetrabromobisphenol A have demonstrated
no estrogenic activity in birds, such as quail and chicken embryos [103]. This apparent deficiency in estrogenic characteristics might be owing to the prompt biotransformation of tetrabromobisphenol A in vivo, as revealed in both rats [104] and
quail [105].
Conclusions
Fire has played a major role in shaping human society and is an essential component
of many religions and ancient mythologies. Stopping or retarding unwanted fire has
always been desired; this coupled with advances of chemical know-how, we have a
variety of chemical substances for this specific task, known as fire retardants. With
T. Hussain et al.