Agent Orange Dioxin Studies Released

Study 1: Dioxins are the most concerned environmental pollutants. Recent studies have shown that these compounds could disrupt the proper functioning of our endocrine system. Estrogen is synthesized in glial cells of the brain. The hormone has been linked to the maintenance of normal brain operation, ranging from neurotransmission to synapse formation. Aromatase or CYP19 is the enzyme responsible for estrogen synthesis. In the present study, we demonstrated that 2,3,7,8-tetrachloro-dibenzo-para-dioxin (TCDD) stimulated the enzyme activity in human brain cells as low as 1 pM. Increased brain-specific CYP19 mRNA species was also observed in these cells. Since the brain-specific promoter I.f of CYP19 contains two binding motifs for CCAAT/enhancer binding protein, electrophoretic mobility shift assay was performed to validate the activation. We further traced the triggering signal and found that the mitogen-activated protein kinases ERK-1/2 were activated. In summary, TCDD could induce CYP19 transcription in brain cells. Exposure to the pollutant might perturb the hormonal balance in the brain.

Study 2: In 1997 the International Agency for Research on Cancer (IARC) classified 2,3,7,8-tetra- chlorodibenzo-p-dioxin (TCDD; the most potent dioxin congener) as a group 1 carcinogen based on limited evidence in humans, sufficient evidence in experimental animals, and extensive mecha- nistic information indicating that TCDD acts through a mechanism involving the aryl hydro- carbon receptor (AhR), which is present in both humans and animals. The judgment of limited evidence in humans was based primarily on an elevation of all cancers combined in four industrial cohorts. The group 1 classification has been somewhat controversial and has been challenged in the literature in recent years. In this article we review the epidemiologic and mechanistic evidence that has emerged since 1997. New epidemiologic evidence consists primarily of positive exposure– response analyses in several of the industrial cohorts, as well as evidence of excesses of several spe- cific cancers in the Seveso accident cohort. There are also new data regarding how the AhR func- tions in mediating the carcinogenic response to TCDD. The new evidence generally supports the 1997 IARC classification. Key words: carcinogen, dioxin, TCDD. Environ Health Perspect 112:1265–1268 (2004). doi:10.1289/ehp.7219 available via http://dx.doi.org/ [Online 10 June 2004]

Read Study 1: http://www.scribd.com/doc/207202936/Molecular-and-Cellular-Endocrinology

Read Study 2: http://www.scribd.com/doc/207203840/Dioxin-Revisted

Molecular and Cellular Endocrinology

http://www.sciencedirect.com/science/article/pii/S0303720713002220

Dioxin Revisted

http://monographs.iarc.fr/ENG/Monographs/vol100F/mono100F-27.pdf