Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes

Summary The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enhance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.Acknowledgment. I am deeply grateful to Dr M.J.W. Faed, for stimulating discussions, guidance and constructive criticism. This paper is a part of my Ph.D. thesis submitted to Dundee University.     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes.

The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enchance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.     

The effects of antineoplastic agents of the respiratory activity of murine lymphocytic leukemia L1210

Résumé On a évalué des effets de plusieurs agents antinéoplastiques sur la consommation d'oxygène des lymphocytes leucémiques L1210 de la souris et on les a mis en corrélation avec l'activité antitumorale de chaque composition. Cette étude indique qu'il n'y a pas de rapport apparent entre ces deux paramètres de l'action des drogues.

---

---

Acknowledgments: The authors wish to express their appreciation to Dr.R. M. Folk of Battelle's Columbus Laboratories for his consultation and advice and toMelanie Crossin for her technical assistance.

---

Supported by Grant No. AM-HE-12084-15 from the National Institutes of Health, Bethesda, Maryland, and Grant No. 7132 from The Ohio State University General Research Support Fund.     

Flavonoid wing pigments in grasshoppers

Yellow pigments extracted from the hindwings ofDissoteira carolina (L.) (Acrididae:Oedipodinae) were identified by HPLC, GLC, MS and absorbance spectra as primarily quercetin and quercetin--3-O-glucoside with minor amounts of luteolin. These flavonoids make up about 2% of the hindwing live weight and are also abundant in the yellow hindwings of several related species of band-winged grasshoppers. Fat body UDPG glucosyltransferase preferentially catalyzed glucosylation of the 3-OH of quercetin.     

Tumor necrosis factor as an antineoplastic agent: pitfalls and promises

The discovery and cloning of the cytokine tumor necrosis factor α (TNF) gave rise to new hopes for a significant victory in the war against cancer. Preclinical in vitro studies in cell cultures and in vivo studies in animal models demonstrated the antitumor capacities of TNF. Although clinical studies were largely made possible by the availability of recombinant TNF, phase I and II clinical trials showed very quickly that the systemic administration of TNF induced severe side effects mainly due to its pleiotropic action on immunocompetent cells. The clinical manifestations of the side effects were similar to those observed during a severe infection and inflammation. Very recently, lessons from these clinical studies yielded refined approaches whereby the toxicity of TNF is limited through local administration, a combination with other therapeutic regimens and targeted gene therapy. These new approaches are slated for larger clinical trials and in the near future might demonstrate the limited but powerful usefulness of TNF as an antineoplastic agent for different types of cancer. Received 7 September 1998; received after revision 15 October 1998; accepted 15 October 1998     

Temperature-dependent responses to a developmental gradient in theDrosophila wing

Summary The mutant hairy (h) increases the number of sensillae on theDrosophila wing. This allows us to quantify a gradient that determines the type of sense organ that forms along the third long vein. Temperature significantly shifts the positional responses to this underlying gradient.This research was supported by National Science Foundation grant BSR-8300025. We thank Laura Karcher for the figure.     

Genotoxic evaluation of ten carcinogens in theDrosophila melanogaster wing spot test

To provide further background data on the wing spot somatic mutation and recombination assay, 10 selected carcinogens (acetamide, acrylamide, benzo(a)pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) were tested in this assay. 72-h-old third-instar larvae, trans-heterozygous for 2 recessive wing cell markers:multiple wing hairs (mwh) andflare ³ (flr ³) were fed with 3 concentrations of each carcinogen during the rest of their development until pupation, and the genotoxic effects were measured as significant increases in the appearance of visible mutant hair clones on the adult wing blade. Our results show that 6 of the carcinogens tested produce significant increases in wing spot frequency, at least at one of the concentrations assayed. Benzo(a)pyrene, diethylstilbestrol, safrole and thiourea were the compounds that did not increase the incidence of mutant clones.     

The isolation and structure of 13,18-dehydroglaucarubinone,a new antineoplastic quassinoid fromSimarouba amara

Summary An investigation of the Guyana plantSimarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.Antineoplastic agents 59. For part 58 refer to M. T. Edgar, G.R. Pettit and T.H. Smith, J. org. Chem., in preparation.Acknowledgments. We wish to thank Mr B. Septe for providing the¹³C-NMR-data. Dr Jean H. Schmidt and Miss Linda M. Lange for assistance with biological studies.—G.R. Pettit is grateful to the National Cancer Institute (performed pursuant to contract No. N01-67048 with the Division of Cancer Treatment, NCI, National Institutes of Health, Dept. of Health, Education and Welfare), Public Health Services Research grant No. CA 16049-03 from the National Cancer Institute, the Fannie E. Rippel Foundation, Talley Industries, and the Phoenix Coca-Cola Bottling Co., for partial support of this investigation.     

Potential carcinolytic agents. VI. New deactivated biological alkylating agents

Résumé Les auteurs ont effectué de nouvelles préparations chimiques anticancéreuses en utilisant une forme des agents alkylants déactivés du type moutarde nitrogénée quaternaire. Un mode d'action est proposé par lequel ces préparations peuvent être activées in vivo.

---

---

Sponsored by the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, Contract No. SA-43-ph-4360.     

Maternal regulation of wing polymorphism inPyrrhocoris apterus: Effect of cold activation

Summary In a macropterous strain ofPyrrhocoris apterus the offspring of females kept under long-day conditions are invariably mostly macropterous, whereas the offspring of females from short-day conditions become macropters under long-day and brachypters under short-day conditions. The brachypterizing effect of short days was removed by the chilling of mothers for 70 days.     

Complexing agents from microorganisms

Summary The majority of extracellular complexing ligands produced by microorganisms are summarized as being of low molecular mass (<10,000 daltons) and are usually released as part of metal detoxification processes. These exudates appear to exhibit strong metal-binding characteristics, often reducing metal toxicity. Under certain conditions microbes produce metal-specific compounds of low molecular mass called siderophores; although these are normally specific for iron they also have relatively high affinities for radionuclides such as Pu and facilitate their uptake into cells. The occurrence of specific actinide complexing agents has been recorded.The breakdown of lignins and cellulosic material produces large macromolecular compounds called humates. These contain multiligand sites and display a wide range of complexing abilities. They form both soluble and insoluble complexes with toxic elements with various results. Humates also considerably influence adsorption of metals to substrate surfaces and at high pH may compete with OH-ions for metal binding.As well as with extracellular ligands, metals can interact directly with microorganisms by accumulation in subcellular compartments or by adsorption on bacterial surfaces.     

An antineoplastic C14-labeled methylhydrazine derivative in P815 mouse leukemia. a metabolic study

Zusammenfassung Die endst?ndige N-Methyl-Gruppe von 1-Methyl-C¹⁴-2-p-(isopropylcarbamoyl)benzylhydrazin-Hydrochlorid (MBH) (Ro 4-6467) erwies sich in In-vivo-Experimenten metabolisch labil, wird teilweise oxydiert und Bestandteil des Formiatpools.      

Bacterial endotoxins as immunosuppressive agents

Zusammenfassung Der Adjuvanseffekt von bakteriellem Endotoxin gegenüber Schaferythrocyten war nicht nachweisbar, wenn Mäuse vor der primären antigenen Stimulierung 9 Tage lang eine tägliche Injektion von 20 µg Endotoxin erhielten. Andererseits wurde unter diesen Bedingungen eine Primärreaktion gefunden, wie sie nach alleiniger Injektion des Erythrocytenantigens zur Ausbildung gelangt. Die Zahlen an 19S- und 7S-Antikörper bildenden Zellen sowie die Serumantikörpertiter waren jedoch signifikant vermindert, wenn vor Applikation der immunisierenden Injektion höhere Dosen von homologem oder heterologem Endotoxin gegeben worden waren.