POP levels in breast milk and maternal serum and thyroid hormone levels in mother-child pairs from Uppsala, Sweden.

In experimental studies, it has frequently been observed that the homeostasis of thyroid hormones (THs) is affected by exposure to persistent organic pollutants (POPs), such as dioxins and PCBs. In man, similar effects have been indicated in several epidemiological studies. In order to investigate the possible effect on THs at low background exposures found among the Swedish population the following study was performed. Primiparous women (n=395) in the Uppsala region were recruited between 1996 and 1999. Of these, 325 mothers agreed to donate a serum sample in late pregnancy and breast milk was obtained from 211 women 3 weeks after delivery. Babies were sampled for blood at 3 weeks (n=150) and 3 months (n=115) after birth. In connection to the sampling, questions on personal characteristics were asked. Levels of low (tri- to penta-) chlorinated PCB, di-ortho PCB, p,p'-DDE, (mono-ortho) PCB TEQ and PCDD/DF TEQ were monitored in breast milk and in mother's blood (not PCDD/DF). The results showed that the measured TH levels (thyroid-stimulating hormone - TSH, total tri-iodothyronine - TT3, free thyroxine - FT4) in mothers and children were within the reference range. Some significant associations were seen between POP exposures and TH levels in mother or child after simple regression analysis. Following adjustment for important confounding factors, the significant associations mostly disappeared. However, significantly decreasing TT3 levels with increasing prenatal low-chlorinated PCB exposure were still seen in 3 week old children, and on TT3 in mothers exposed to PCDD/DF. In conclusion, the study clearly shows the importance of adjustment for important confounding factors in the analysis of possible associations between POP exposure and hormonal effects. The remaining associations are weak in both children and mothers and the clinical consequences of these alterations are uncertain. When comparing studies that investigate associations between TH levels and POP levels during the perinatal stage, no obvious between-study concordance was seen regarding the critical dose for hormonal effects to occur.

Inhibition of Raf-1 kinase expression abolishes insulin stimulation of DNA synthesis in H4IIE hepatoma cells.

The involvement of Raf-1 kinase in the insulin signal transduction chain leading to control of cell proliferation was studied in the H4IIE rat hepatoma cell line by inhibiting expression of the kinase with antisense oligodeoxyribonucleotide directed against Raf-1 mRNA. Antisense oligonucleotide was found to reduce (at 2 microM) or completely block (at 15 microM) the stimulation by insulin of DNA synthesis, measured as thymidine incorporation. The residual DNA synthesis seen in the absence of insulin stimulation was also inhibited by the Raf-1 kinase antisense oligonucleotide.