Carcinogenicity and metabolic activation of hexestrol

The carcinogenic activity of the synthetic estrogen hexestrol was measured in male Syrian hamsters. Between 90% and 100% of the animals treated with hexestrol or with 3',3",5',5"-tetradeuteriohexestrol, implanted subcutaneously as 25-mg pellets, were found with renal carcinoma after 6-7 months. In vitro hexestrol metabolism, mediated by phenobarbital-induced rat liver microsomes, led to the formation of 3'-hydroxyhexestrol. This metabolite was identified by comparison with authentic reference material synthesized by oxidation of hexestrol with Fremy's salt. Diethylstilbestrol could not be detected as a metabolite. In urine of male Syrian hamsters, 3'-hydroxyhexestrol, 3'-methoxyhexestrol, 1-hydroxyhexestrol, and other hydroxylated and/or methoxylated hexestrol metabolites were identified. Again, diethylstilbestrol was not detectable as a hexestrol metabolite in vivo. The reactivity of 3'-hydroxyhexestrol was then studied to determine if this catechol estrogen played a role in hexestrol carcinogenicity. Horseradish peroxidase catalyzed the oxidation of 3'-hydroxyhexestrol to 3',4'-hexestrol quinone. This oxidation reaction could also be carried out non-enzymatically using silver oxide or silver carbonate on celite as oxidants. The quinone was unstable (t1/2 in methylene chloride: 53 min). It reacted with sulfur-containing compounds such as mercaptoethanol by Michael addition to form 3'-(2-hydroxyethylthio)-5'-hydroxyhexestrol. 3',4'-Hexestrol quinone reacted with simple amines such as ethylamine to form N-ethyl-aminohexestrol. The chemical reactions described above were carried out to test the reactivity of identified or suspected metabolic intermediates of hexestrol. It was concluded that carcinogenicity of hexestrol was not based on its conversion to diethylstilbestrol. Rather, catechol estrogen formation may be necessary for the carcinogenic action of hexestrol in analogy to events observed earlier with estradiol.     

Enzyme immunoassay for the determination of hexestrol in meat

An indirect competitive enzyme-linked immunosorbent assay (ELISA) of hexestrol (HES), an anabolic hormone forbidden for use in livestock farming, has been developed. Conditions of ELISA have been optimized by varying the concentrations of the coating conjugate (HES-ovalbumin), anti-HES antiserum, casein, and Tween 20. In the absence of Tween 20 in the reaction mixture, the detection limit (IC₁₀) equaled 0.01 ng/ml, IC₅₀ equaled 0.17 ng/ml, and the working range (IC₂₀–IC₈₀) equaled 0.03–0.86 ng/ml, while, in the presence of 0.05% Tween 20, these values equaled 0.05, 2.9, and 0.26–32.0 ng/ml, respectively. Standard deviation of the analysis results did not exceed 5.4%. If ELISA was performed in the absence of detergents, the recovery value upon HES determination in spiked beef samples ranged from 74 to 147%.     

On the direct effect of clouds and atmospheric particles on the productivity and structure of vegetation

The volume of shade within vegetation canopies is reduced by more than an order of magnitude on cloudy and/or very hazy days compared to clear sunny days because of an increase in the diffuse fraction of the solar radiance. Here we show that vegetation is directly sensitive to changes in the diffuse fraction and we conclude that the productivity and structure of vegetation is strongly influenced by clouds and other atmospheric particles. We also propose that the unexpected decline in atmospheric [CO₂] which was observed following the Mt. Pinatubo eruption was in part caused by increased vegetation uptake following an anomalous enhancement of the diffuse fraction by volcanic aerosols that would have reduced the volume of shade within vegetation canopies. These results have important implications for both understanding and modelling the productivity and structure of terrestrial vegetation as well as the global carbon cycle and the climate system.     

The direct effect of the thyroid hormone on cardiac chronotropism

To establish whether thyroid hormone modifies the heart rate directly or through an action on other neuroendocrine modulators, the authors have examined several animals models differing in the plasma levels of such compounds. Induction of the hypothyroid state in rats produced a slow onset of bradycardia, which may be removed by a prolonged triiodothyronine treatment. The involvement of TSH was excluded as, by comparing thyroidectomized, hypophysectomized and cold exposed rats, the heart rate was found to vary according to the thyroid levels and not to the TSH levels. Moreover growth hormone, corticotropin and gonadotropins do not influence the heart rate, as the bradycardia induced by hypophysectomy was fully removed by triiodothyronine treatment. The lack of influence by ACTH and GnH was confirmed by treatment of thyroidectomized rats with corticosteroids or testosterone, respectively. Finally, thyroid hormone did not act on the heart rate by changing the norepinephrine output at the sympathetic nerve endings in the heart. In fact, thyroidectomy produced a more intense bradycardia than sympathectomy, and such bradycardia was equally removed by triiodothyronine treatment in thyroidectomized rats and in thyroidectomized and then sympathectomized ones. The authors suggest that the direct effect of the thyroid hormone on cardiac chronotropism is due to an early enhancement of beta-adrenoceptors, followed by a late modification of the electrophysiological properties of the myocardium.     

The effect of leaf-lobing on the interception of direct solar radiation

Summary The extent to which leaf-lobing influences the interception of direct solar radiation by individual plants was studied by means of computer simulations. The morphology, size and orientation ofAmbrosia artemisiifolia L. leaves were measured and used to construct a prototypeAmbrosia plant upon which a computer simulation was based. The leaf geometries of this simulation were then varied, and daily integrated irradiances (DII) were calculated for each variant plant simulation. Data indicate that lobedAmbrosia leaves do not confer an advantage to light-interception based upon values of DII. Simulated plants identical in all respects to the prototype, but with simple, elliptic leaves, had equivalent DII values to the prototype. Simulations with leaves in which gaps between lobes were filledin had reduced light-interception efficiencies compared to the prototype and to a simulation with elliptic-leaves. Lightinterception was maximized when leaves on distal nodes wereAmbrosia-like and leaves on proximal nodes were elliptic. The data are interpreted to indicate that lobingperse is not functionally advantageous to light-interception; however, gradients of leaf-lobing along the length of shoots may be very significant in terms of overall light interception.     

Possible direct effect of diethylcarbamazine on the infective larvae of Brugia pahangi

The direct action of diethylcarbamazine (DEC) on the infective larvae of Brugia pahangi was studied. The larvae were cultured in RPMI 1640 supplemented with foetal bovine serum and antibiotics for 22 days. Most of the larvae remained alive for 8 days, but survival rate of larvae decreased rapidly from day 10 onwards. The larvae did not grow in the culture system. The addition of DEC did not affect the morbidity of the larvae and no difference was observed in the morphological characteristics between the larvae cultured in the presence or absence of DEC. The infective larvae were cultured in vitro for 5 days in the presence or absence of DEC, and inoculated into jirds. The animals were necropsied at intervals, and developing larvae and adult worms were recovered. When the larvae were cultured without DEC and then inoculated subcutaneously into jirds, 29.8% of the inoculum was recovered 3-15 days, and 25% 19-22 weeks, post-inoculation. However, when the larvae were exposed to DEC in vitro and inoculated into jirds, the rate of recovery was reduced to 25% 3-15 days post-inoculation and 2% after 19-22 weeks. When the control larvae cultured in vitro were inoculated intraperitoneally into jirds, 41.3% of inoculum was recovered 3-15 days, and 42.8% 19-22 weeks, post-inoculation. Again the corresponding value for larvae exposed to DEC in vitro was reduced to 19.8% 3-15 days, and 8% 19-22 weeks, post-inoculation. It was observed that the larvae exposed to DEC in vitro were retarded in their development in jirds.(ABSTRACT TRUNCATED AT 250 WORDS)