The effect of chlorination of estrogenic chemicals on the level of serum vitellogenin of Japanese medaka (Oryzias latipes).

Mature male medaka were continually exposed to four chemicals, p-n-nonylphenol (p-n-NP), nonylphenol (p-NP), bisphenol-A (BPA) and 17beta-estradiol (E2) to evaluate their estrogenic activities in the laboratory. In order to understand the effect of the chlorination that is applied widely in water and wastewater treatment, the above chemicals were chlorinated and then exposed to mature male medaka. Furthermore, in the case of vitellogenin, a is a female specific protein induced by the exposure to test waters containing the above chemicals after 5 weeks, medaka was returned to uncontaminated tap water to determine whether male medaka have a self recovery function from the effect of estrogenic chemicals. Much greater vitellogenin compared to the background levels were induced in the male medaka by separate exposure to 100 microg/L of p-NP, 1,000 microg/L of BPA and 0.05 microg/L of E2. The levels of vitellogenin increased with increasing exposure periods. The relative potencies of these chemicals descended in the order of E2>>p-NP>BPA. Vitellogenin levels inducible by these chemicals were drastically reduced as a result of the chlorination for 24 hours. However, a moderate increase in hepatocyte somatic index (HSI) meant the hepatic fatness was observed as a result of chlorination. It is not clear at this stage whether or not the formation of chlorination byproducts is responsible for this moderate increase in HSI. The vitellogenin concentration of male medaka exposed to chemicals for 5 weeks decreased gradually after return to the uncontaminated water. However, the vitellogenin concentration did not return to the initial normal levels even after 5 weeks. A clear relationship between the serum vitellogenin concentration and the hepatic vitellogenin concentration was also found. Since quantitative analytical procedures for hepatic vitellogenin are easier than those of the serum vitellogenin, measuring the estrogenic effect using the measurement of vitellogenin in liver is recommended.

Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development.

Oestrogens, including the natural hormones oestrone and oestradiol, induce various tumours in laboratory animals and have been recognized to be carcinogens in humans, raising the risk for breast and uterine cancer. As part of the search for the mechanism of hormone-induced carcinogenesis, various types of DNA damage have been detected which have been induced by oestrogens in cell-free systems, in cells in culture, or in vivo. Nevertheless, oestrogens have been postulated to act only as promoters of mammary carcinogenesis by receptor-mediated growth stimulation without consideration of their genotoxicity because these hormones failed to induce mutations in commonly used assays. More recently, oestradiol-induced numerical chromosomal changes (aneuploidy) and structural chromosomal aberrations have been detected in cells in culture and in hamster kidney, a target of oestrogen-induced cancer. In this animal model, oestradiol generates c-myc gene amplification and microsatellite instability. Mutations of the hprt gene have been induced by oestradiol in V79 cells and by catecholoestrogen metabolites in Syrian hamster embryo cells. Sequencing of this gene isolated from V79 mutant clones revealed point mutations and deletions. It is concluded that oestradiol plays a dual role as mutagen/carcinogen and as growth-stimulating hormone in the induction of tumours.

[Thrombus of the aortic arch: an unusual pathology in intensive care]. / Le thrombus de la crosse de l'aorte: une pathologie rare en réanimation.

A 54-year-old patient was admitted to the intensive care unit for voluntary drug intoxication with zolipidem (Stilnox), dimenhydrinate (Mercalm), and oestradiol 17 beta (Oromone). Four hours after the admission the patient was comatose. Cerebral computerized tomodensitometry demonstrated multiple zones of ischaemia. Transoesophageal echocardiography was performed 12 hours after the arrival of the patient and revealed a mobile thrombus of the aortic arch. The remainder of the visualized aortic arch did not present atherosclerotic plaque. Secondarily, ischaemia of the right superior limb was diagnosed probably cause by emboli originating in the aortic thrombus appeared. The patient died three days later after her arrival, because of neurologic sequelae of the cerebral embolic events. This clinical case underlines the concept that the diagnosis of drug intoxication must remain a diagnosis of elimination. The thrombosis of the aortic arch is a rare pathology in intensive care units. In the presence of unexplained ischaemic stroke and an peripheral emboli, the thrombosis of the aortic arch should be suspected.

Effects of a massive single oral dose of oestradiol valerate in a young woman.

Effects of a massive single oral dose of oestradiol valerate were studied in a young woman. A slight increase in serum triglyceride and phospholipid concentrations was seen soon after the oestrogen administration. A marked rise in the serum cortisol concentration was evidently caused by psychic stress on the patient. The EEG examined on the first day after oestrogen administration showed findings typical of subcortical disturbance. One week later the EEG was normal. The low toxicity and slight side effects of a large overdosage of oestradiol valerate by month are worth noting.