Effect of interferon γ and tumour necrosis factor α on sensitivity to cisplatin in ovarian carcinoma cell lines

This study aimed to investigate whether the biological response modifiers (BRM) interferon (IFN) and tumour necrosis factor (TNF) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF and IFN demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.     

The impact of phytoplankton on spectral water transparency in the Southern Ocean: implications for primary productivity

Spectral water transparency in the Northern Weddell Sea was studied during Austral spring. The depth of the 1-% surface irradiance level (euphotic depth) varied between 35 and 109 m and was strongly influenced by phytoplankton biomass. Secchi depths were non-linearly related to euphotic depth. In phytoplankton-poor water, the most penetrating spectral region was restricted to a relatively narrow waveband in the blue (488 nm), but the range was broader, between 488 and 525 nm when phytoplankton were abundant. Water transparency in the red spectral range was always low and only to a small extent affected by phytoplankton. Two independent procedures were used to quantify the impact of phytoplankton on spectral water transparency: (1) Regression analysis of spectral in situ vertical light attenuation coefficients in the sea, against coincident chlorophyll concentrations. This method gave chlorophyll-specific light attenuation coefficients; the y-intercept could be interpreted as a measure of light attenuation by pure water plus non-algal material. (2) Spectra of in vivo light absorption derived by spectroscopy, using phytoplankton enriched to varying degrees onto filters. Thus chlorophyll-specific absorption cross-sections were determined. Estimates obtained by both procedures were in close agreement. By integrating over the spectrum of underwater irradiance, in situ chlorophyll-specific absorption cross sections of phytoplankton suspensions, related to all photosynthetically active radiation, were calculated. Light absorption by phytoplankton for photosynthesis is accomplished mainly in the blue spectral range. Also dissolved and particulate organic matter contributed to the attenuation of blue light. Because in water poor in phytoplankton, underwater irradiance was progressively restricted to blue light, chlorophyll-specific absorption cross-sections of phytoplankton, averaged over the spectrum of photosynthetically active irradiance, increased with water depth. In water with elevated phytoplankton biomass, overall light attenuation was generally enhanced. However, because the spectral composition of underwater light changed relatively little with depth, except immediately below the water surface, light absorption cross-sections of phytoplankton changed little below 10 m depth. Vertical differences in the proportions of underwater light absorbed by the phytoplankton community here were mainly dependent on biomass variations. Because of the comparatively small attenuation of blue light by non-algal matter, the efficiency of light harvesting by phytoplankton at any given concentration of chlorophyll in Antractic waters is greater than in other marine regions. At the highest phytoplankton biomass observed by us, as much as 70% of underwater light was available for phytoplankton photosynthesis. When phytoplankton were scarce, <10% of underwater light was harvested by phytoplankton.Contribution within the European Polarstern Study (EPOS), supported by the Deutsche Forschungsgemeinschaft, Grant Ti 115/16-1 to MMT, the European Science Foundation, and by the Alfred Wegener Institut für Polar-und Meeresforschung, Bremerhaven     

Multinuclear NMR studies of intracellular cations in the prehypertensive rat kidney

We previously reported a significant derangement of intracellular free calcium ion concentration in the isolated perfused kidney of adult spontaneously hypertensive rat (SHR) (J. Biol. Chem. 267, 3637–3643, 1992). In order to investigate whether an abnormality in intracellular free calcium or another ion precedes the development of elevated blood pressure in SHR, we have now compared intracellular free Ca²⁺, Na⁺ and pH, using ³¹P, ¹⁹F, and triple quantum-filtered (TQ) ²³Na NMR, in perfused kidneys from prehypertensive young SHR and normotensive young Wistar-Kyoto (WKY) rats (5–6 weeks old) which showed no significant difference in blood pressure B.P.=120±5 mmHg and 115±3 mmHg, for SHR and WKY rats, respectively). Like the adult kidney, no significant differences in intracellular ATP concentration or intracellular pH were found between young prehypertensive SHR and normotensive WKY rat kidneys. The TQ ²³Na NMR signal was 47% higher in the SHR kidney, but, due to biological variability and measurement errors, this difference could not be shown to be statistically significant. However, a significant (40%; P<0.05) increase was found in O₂ consumption rate, a measure of the Na⁺/K⁺-ATPase activity, of the young prehypertensive SHR kidney in comparison to the age-matched WKY rat kidney (7.25±0.75 for SHR vs. 5.17±0.18 μmola O₂/min g for WKY rat, n = 6). Furthermore, a highly significant (92%; P<0.02) increase in intracellular free Ca²⁺ concentration was observed in kidneys from young SHR that had noy yet been developed high blood pressure in comparison to the kidneys from young normotensive WKY rats (648±76 nM vs. 339±39 nM, n = 4, despite the fact that there was no significant difference in blood pressure. Increased intracellular free Ca²⁺ thus appears to be part of a primary defect, in the prehypertesive young SHR kidney, which may, by way of increased release of arachidonic acid, and subsequent increased production of vasoconstricting arachidonic acid metabolites via the cytochrome P450 pathway, induce elevated blood pressure in the adult SHR.     

Island/mainland body size differences in Australian varanid lizards

Island varanids seem to be an exception to the rule that territorial vertebrate taxa often become gigantic relative to mainland relatives when on islands, whereas non-territorial species become dwarfed (Case 1978). However, no systematic island/mainland studies have examined the empirical size trends in this group of carnivorous lizards. We perform such an analysis for the Australian region and critically evaluate various selective agents that might be responsible for size changes in several island populations. Insular gigantism occurs at least four times among the island populations examined. The magnitude of size change is positively correlated to prey abundance on the islands (as indirectly measured through a condition index of the lizards, essentially a measure of how fat they arc) and the size of prey: islands with large prey have large varanids and vice versa. Since the island population with the largest size change, the Reevesby Varanus rosenbergi, was introduced less than 100 years ago, these size changes can be quite rapid. This might indicate that selective coefficients are strong; however, we can not exclude the possibility that these size differences have no genetic component and simply reflect environmental differences in growth rate and shifts in age structure between island and mainland locations.     

Managing lepidopteran pests in cabbage with herbicide-induced resistance, in combination with a pyrethroid insecticide

S-ethyldipropylthiocarbamate (EPTC) applied as a soil treatment or over-the-top spray on cabbage plants (Brassica oleracea L.) caused the leaves to turn ‘glossy’ for as long as 30 days. EPTC-induced glossy plants were damaged significantly less than untreated plants by diamondback moth,Plutella xylostella (L.), imported cabbage worm,Pieris rapae (L.), and cabbage looper,Trichoplusia ni (Hbn.). Reductions in damage were equivalent to those obtained from treatment with permethrin. When used in combination with permethrin, EPTC provided additive control of damage by these pests. Our calculations show EPTC-induced resistance to be cost-effective. This use of EPTC has several limitations, however. Younger plants (<9 leaves) were killed or injured by the herbicide. The growth of older plants was not affected, but plants did not become glossy for ca. 10 days after they were treated with EPTC. The crop must be protected with insecticides until the plants are mature enough to treat with EPTC, and until treated plants become glossy. In addition, since the glossy trait is only effective against first instar larvae, populations of later instars on glossy plants must be reduced with an application of insecticide. Finally, EPTC formulations are water-soluble and can be washed away from the plants by heavy rains and irrigation, which may make this use of EPTC impractical in some situations. Where its use is practical, and the indicated precautions are taken, EPTC-induced resistance could reduce dependence on chemical insecticides and reduce selection for insecticide resistance in diamondback moth.     

Expression analysis of the mixed function oxidase system in rat brain by the polymerase chain reaction

Metabolism of therapeutic drugs in the body by the mixed function oxidase system is an important consideration in the analysis of a drug's effectiveness. P450-dependent metabolism within the brain of a neuro-specific drug may affect the drug's course of action. To determine whether cytochrome P450 was expressed in brain, RNA was isolated from the whole brains of rats treated with a variety of known hepatic P450 inducers, including amitriptyline, imipramine, isosafrole, phenobarbital, and -naphthoflavone. The RNA was analyzed for the presence of P450 isozymes by the PCR technique. Differential expression of P450IA1, P450IIB1, P450IIB2, P450IID, and P450IIE1 was detected in the brain samples, depending on the treatment. Cytochrome P450 reductase expression was also detected in the brain samples, giving strong evidence that the brain contains a competent mixed function oxidase system under all conditions studied. (Mol Cell Biochem120: 171–179, 1993)Thesis student of the Graduate School of Biomedical Sciences, the University of Texas Health Science Center at Houston     

Somatic embryo maturation from long-term suspension cultures of white spruce (Picea glauca)

Summary The production of cotyledonary somatic embryos of white spruce from cultures grown long-term as suspensions was investigated. We report the effects of removal of 2,4-dichlorophenoxyacetic acid (2,4-D) from the maintenance medium (ordinarily containing both 2,4-D and benzyl adenine) before (&#x00B1;)-ABA-stimulated maturation. In particular the use of a 1-wk culture period without 2,4-D was found to improve the production of normal-looking cotyledonary somatic embryos. Using high performance liquid chromatography analyses of culture supernatants, it was determined that this affect was not related to altered ABA metabolism. Germination of cotyledonary somatic embryos from cultures pretreated by the 1-wk culture period without 2,4-D was improved compared with similar embryos from cultures that had not been pretreated.     

In vitro characterization of estrogen induced syrian hamster renal tumors: Comparison with an immortalized cell line derived from diethylstilbestrol-treated adult hamster kidney

Summary Primary diethylstilbestrol-induced kidney tumors from Syrian hamsters were grown in vitro and maintained in culture for 6 mo. Combined immunohistochemical studies using antibodies to intermediate filaments and ultrastructural studies of tumor cells in culture exhibited characteristics similar to tumor cells in vivo. Furthermore, the cells manifested transformed properties in culture; they grew both as multilayered colonies attached to the tissue culture substrate and as floating multicellular colonies (spheroids). When cultured cells were injected into diethylstilbestrol-treated recipient hamsters, tumors developed at the injection sites. In contrast, renal tubules or whole kidney cortex from control hamsters cultured in the same medium underwent only short-term growth, with senescence developing after approximately 1 mo. However, cell cultures of kidney cortex from animals treated in vivo for 5 mo. with diethylstilbestrol formed a cell line. This diethylstilbestrol-induced cell line has been maintained in culture for 1.5 yr and has the following characteristics: a) it is anchorage-dependent, b) it is negative in in vivo tumorigenicity tests, and c) cultured cells are histochemically and ultrastructurally similar to cultured tumor cells. This culture system should prove to be of use in studying hormonal carcinogenesis in vitro. This study was supported by the Medical Research Service, Department of Veterans Affairs, Washington, DC, and by grant CA-22008 from the National Cancer Institute, NIH, DHHS, Bethesda, MD.