The mitigating effect of dietary antioxidants on chemically-induced carcinogenesis

Summary The effect of a dietary antioxidant mixture on 3-methylcholanthrene mediated carcinogenesis in hairless mice was investigated. The antioxidant mixture significantly reduced the frequency of premalignant lesions and their subsequent development into tumors. The similarities in response of chemical and UV light-carcinogenesis to these antioxidants suggest some congruity in the mechanisms of the carcinogenic process.This investigation was supported by National Research Service Award 1 F32 CA05062, awarded by the National Cancer Institute, DHEW and USPH grant CA13464 from the NCI, DHEW. We thank Dr John I. Thornby for statistical analysis of the data.     

Vitellogenin synthesis induced in locust fat body by juvenile hormone analog in vitro

Summary Fat bodies from adult females ofLocusta migratoria continue to synthesize vitellogenin and other proteins when cultured in vitro. A strong secondary induction of vitellogenin synthesis was obtained in fat bodies cultured in the presence of methoprene, and a weaker but significant primary induction was also obtained using higher doses (>100 g) of methoprene.This work was carried out in Dr G.R. Wyatts Laboratory and I thank him for helpful discussions. I also thank Dr G. Staal (Zoecon Corp.) for supplying the methoprene and Pfizer Inc. for rimocidin sulfate. This research was supported by grants from the US NIH (HD 02176) and Canada NSERC.     

Paroxysmal discharges in the electroencephalogram of the El mouse

Summary The spike discharges in the EEG of the El mouse, a seizure-susceptible strain, were recorded during convulsive seizures. This fact provides evidence that those seizures are really epileptic convulsions.I thank Dr.K. Imaizumi and Dr.K. Nakano of National Institute of Health for their sharing the strain of El mouse to us and MissY. Nakamoto and Mr.N. Ozawa for their technical assistance and Mr.K. Moriyama for his care for the mice, and also thank Dr. H.Narabayashi for his criticism on this paper.     

Evolutionary implications of ascorbic acid production in the Australian lungfish

Summary It is shown that the Australian lungfish (Neoceratodus forsteri) synthesizes ascorbic acid in its kidney, suggesting that ascorbic acid synthesis started before the origin of the tetrapods.Acknowledgments. We would like to thank Dr G.C. Grigg, University of Sydney, Mr R. B. Humphries, Dr P.A. Janssens and Dr C.H. Tyndale-Biscoe, Australian National University, and Dr. M. Griffiths and J.C. MacIlroy C.S.I.R.O., Division of Wildlife Research for supplying the tissue.     

The membrane attack complex ofXeopus laevis complement

Summary Rabbit erythrocyte membranes lyzed byXenopus laevis serum exhibited a typical ultrastructural complement lesion with an inner diameter of 80±9Å. The protein pattern associated with lyzed membrane is compared to a similar human preparation.Acknowledgments. I wish to thank Dr. I. Hadji-Azimi for her interest and encouragement, and Professor N. Parrinello for critical reading. This work was supported by a grant from the Swiss National Science Foundation (3.083–0.84).     

Effects of palytoxin on the electrical activity of dog and rabbit heart

Summary Reversible effects of palytoxin, extracted from colonies of the soft coralPalythoa caribaeorum, are described. There is a decrease of both membrane resting potential and overshoot during activity. Rise time of the action potential is prolonged, while repolarization is shortened. The electrical events resemble those seen with metabolic poisons.This work was supported by grant 10897 from the National Heart and Lung Institute, Bethesda, Md., and by grant 3.758. 72 from the Swiss National Science Foundation.I wish to thank Dr W. C. De Mello for hospitality in his department, Dr T. Morales for allowing me to use his equipment, Dr. J. Santos Martínez for providing me with hearts of poisoned and unpoisoned dogs, and Drs E. Toro-Goyco and A. M. Preston of the Department of Biochemistry for letting me have a sample of toxin.     

A simple method for the preparation of antibodies to the mitochondrial biotin-dependent carboxylases

Summary Heterologous antiserum to the 3 biotin-dependent carboxylases was prepared by selective removal of these enzymes from human liver on an avidin-sepharose column. A carboxylase-avidin-sepharose matrix was used as an antigen to produce anti-carboxylase antibodies. The resultant antisera can be used to purifiy the specific carboxylases, to prepare monoclonal antibodies to these enzymes or to study inherited carboxylase deficiencies and biotin-dependent intermediary metabolism.The authors thank Dr Emmanuel Shapira for his helpful suggestions and Patricia Tuck for her technical assistance. This work was supported by NIH research grants AM25675 and AM26127. Barry Wolf is a recipient of an NIH Research Career Development Award (AM00677) and is aided by a Basil O'Connor Starter Research Grant from the National Foundation—March of Dimes (5–263). This is paper No. 137 from the Department of Human Genetics — Medical College of Virginia.     

Photoreceptor properties of an ectopic eye in the fleshfly,Sarcophaga bullata

Summary Ectopic eyes were produced on the fleshfly,Sarcophaga bullata by transplantation of imaginal eye discs. Electrophysiological and histological observations of these supernumerary eyes indicate the absence of synaptic connections between retinular cells and higher order neurons.Supported by an University of New Brunswick research grant to P.S. and NSF grant BNS-76-11921 and NIH grant 1-R01-EY-02487-01A1 to W.S.S.We would like to thank Dr I.A. Meinertzhagen for suggestions and Mary Johnson for technical assistance.     

Enantiomeric cannabinoids: stereospecificity of psychotropic activity

Summary The 1,1-dimethylheptyl homolog of (–)-(3R,4R)-7-hydroxy-delta-6-tetrahydrocannabinol (compoundII) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED₅₀ of (II).We thank Dr A. Breuer and Mrs H. Amsalem for help with the syntheses. The research reported above was supported in Tucson by NIH grant NS 15441; in Uppsala by grants from the Swedish Medical Research Council (5757) and the Swedish Council for the Planning and Coordination of Research (84/2082); in Jerusalem by the Szold Foundation.Presented in part at a meeting at the US National Institute on Drug Abuse, Washington, D.C., October 1986, see NIDA Research Monographs79 (1987) 15.     

Effect of substrates on the mechanical performance of rhesus monkey papillary muscle

Summary This study examines the effect of different substrates on mechanical performance of excised papillary muscles from rhesus monkeys which had been divided into a control group and an experimental group fed a high fat diet for 5 months prior to sacrifice. The results show that performance is affected by available substrate for both groups. The performance of the experimental group was depressed relative to control with the short chain fatty acid, butyrate (C4), producing a monotonically decreasing force-frequency response. Relative to other mammals, isolated rhesus papillary muscles exhibited a protracted treppe which was sensitive to -adrenergic blockade with propranolol.Acknowledgments. I would like to thank Dr R.M. Larson, Dr R.L. McCann and Dr O.F. Hagan for making available the papillary muscles used in this study. Support for this work was provided in part by a grant from the Walker P. Inman Fund and grants from the NIH HL 17391 and HL 15448.     

Freeze tolerance in the frog,Rana sylvatica

Summary Wood frogs survive extracellular freezing at moderate subzero temperatures (–4°C) for at least 11 days. Freezing survival is aided by the accumulation of high concentrations of glucose as a cryoprotectant in blood and tissues. Glucose production was accompanied by a rapid decline in liver, but not muscle, glycogen levels suggesting that liver is the organ controlling cryoprotectant synthesis.Acknowledgments. This study was supported by grants to L.M.G. from the Kroc Foundation (Santa Ynez, California) and from the National Institute of Dental Research (Grant No. DE-03987). The authors wish to thank K. Yorko, M. Shakin, J. Finan and Mrs N. Manivannan for their technical and secretarial assistance.Acknowledgments. I thank Dr J. Ballantyne, Dr F. Schueler and I. McMurray for help with frog collections and Dr. W. Schmid, Dr J. Bogart and Dr F. Cook for helpful discussions. Supported by an N.S.E.R.C. operating grant and by a grant from the Atkinson Charitable Foundation.     

Ansamitocin P-3, a maytansinoid,fromClaopodium crispifolium andAnomodon attenuatus or associated actinomycetes

Summary Guided by cytotoxicity, ansamitocin P-3, a maytansinoid, was isolated in very low yield from two members of the moss family Thuidiaceae,Claopodium crispifolium (Hook.) Ren & Card. andAnomodon attenuatus (Hedw.) Hueb. Ansamitocin P-3 showed potent cytotoxicity against the human solid tumor cell lines A-549, HT-29. A possible basis for the occurrence of this compound in mosses is discussed.Presented at the XV International Symposium on Natural Product Chemistry, Monterrey (Mexico) April 28–30, 1988 and at the International Research Congress on Natural Products, Park City (Utah, USA) in July 1988.Acknowledgments. This work was supported by grant No. CA 33326 from the NCI, NIH, USA. K.S. is the recipient of support from the Anandha-Mahidol Foundation, Thailand. The 470 MHz NMR instrument was available through the Purdue University Biochemical Magnetic Resonance Laboratory supported by NIH grant No. RR1077 from the Biotechnology Resources Program of the Division of Research Resources. Special thanks are due to the Purdue Cell Culture Laboratory for in vitro testing data and to Dr M. Antoun forC. crispifolium extraction. The animal testing data are the results of screening performed under the auspices of the Developmental Therapeutics Program, Division of Cancer Treatment, the NCI.     

Mutagenicity and toxicity of chloroethylene oxide and chloroacetaldehyde

Summary Exposure of severaltrp-auxotrophicEscherichia coli strains, carrying base0pair substitutions, to chloroethylene oxide or chloroacetaldehyde (two metabolites of vinyl chloride) increased the mutation frequency to tryptophan prototrophy. Strong cytotoxic and mutagenic effects were observed with 2.5 mM chloroethylene oxide, while a higher concentration of chloroacetaldehyde (100 mM) exhibited a mutagenic effect which was 400 times lower.I am grateful to Prof. G. Michel, Laboratoire de Biochimie Microbienne, and to Dr H. Bartsch, International Agency for Research on Cancer, for the support of this work. I wish to thank Dr F. Besson-Simien and Dr A. Barbin for their collaboration.     

The infectivity of polyhedra of nuclear polyhedrosis virus (N.P.V.) after passage through gut of an insectpredator

Summary Polyhedral inclusion bodies (P.I.B.) of a nuclear polyhedrosis virus ofHeliothis punctigera (Lep.) were found in excreta ofNabis tasmanicus (Het.), a predator ofH. punctigera. An immunofluorescent counting method was used to estimate numbers of P.I.B. Bioassays demonstrated that no loss of infectivity occurred during passage through the gut.Acknowledgment. I am grateful for the comments and criticism offered by Dr D.E. Pinnock, I thank D.J. Cooper for preparation of materials for the immunofluorescent counting method and J. Hardy for supplying me with eggs ofH. punctigera; all of Department of Entomology, Waite Agricultural Research Institute, Glen Osmond, South Australia.     

Increase in acid phosphatase activity during fertilization of a teleost egg

Summary Acid phosphatase activity was localized at the periphery of the yolk globules in the egg of the teleost,Catostomus commersoni. In addition, a 3-fold increase in acid phosphatase activity was associated with fertilization and pronucleus formation.I thank Dr C. W. Huver for use of facilities.     

The in vitro characterization of the inhibition of mouse brain protein kinase-C by retinoids and their receptors

Summary The mechanism of the in vitro inhibition of Ca²⁺-, phosphatidylserine-dependent protein kinase C (PK-C)² by the purifiedholo (ligand-saturated) forms of cellular retinol-binding protein (cRBP) and cellular retinoic acid-binding protein (cRABP) was studied. We report here that i) the PK-C-inhibitory action ofholo-cRBP andholo-cRABP is due to their respective ligands, all-trans-retinol and all-trans-retinoic acid; ii) the reduced phosphorylation of theholo-retinoid-binding proteins and brain cytosolic proteins is not the result of a retinoid-induced soluble phosphatase or protease activity; iii) retinoids reduce PK-C affinity for calcium and phosphatidylserine in vitro; and iv) the structure-function activity of the retinoids and the specific interaction of these effect of retinoids on plasma membrane-associated PK-C activity pays a significant role in defining the early epigenetic aspects of PK-C-dependent tumor promotion and may be a physiological mechanism by which retinoids induce terminal differentiation in cell types that do not express soluble retinoid-binding proteins.We would like to thank Dr L.M. De Luca (NIH, USA) for his contribution of retinylphosphate, Dr H.N. Bhagavan (Hoffmann-La Roche) for his contribution of the arotinoids, and Merrill-Dow Corp. for their contribution of difluoromethylornithine. This work was supported by NIH Grants CA-34968, CA-07175, CA-22484, and CA-09020.     

Development of intratesticular implants of rat pituitary primordia

Summary Intratesticular grafts of pituitary primordia from 11–13-day-old rat embryos developed in 6 weeks into round nodules approximately 1 mm in diameter. The nodules were principally composed of well differentiated glandular and nervous tissues.We wish to thank Dr Truls Brinck-Johnsen for his kind assistance. This study was supported by the Norris Cotton Cancer Center, Hanover, New Hampshire, and NCI Grant IR25-CA19379-01 CEC.     

Linderazulene,a new naturally occurring pigment from the gorgonianParamuricea chamaeleon

Summary The purple pigment of the gorgonianParamuricea chamaeleon has been isolated and identified as linderazulene (I).We thank Dr K. Takeda for linderazulene spectra, and NATO for a grant (to S.I. and R.H.T.) in support of this work.     

Potentiation of the biological activities of daunomycin and adriamycin by ascorbic acid and dimethylsulfoxide

Summary L-Ascorbic acid (0.57 mM) and dimethylsulfoxide (14.1 mM) were found to potentiate four times the antibacterial activities of daunomycin and adriamycin in theStaphylococcus aureus test. This effect, however, could not be demonstrated against eukaryotic cells and leukemia P388 in mice. The authors thank Dr A. Maráz, Department of Microbiology, J.A. University, Szeged, and Dr Zs. Somfai, Institute of Oncology, Budapest, for collaboration in the experiments with yeast and tumor cells.     

Tyrosine hydroxylase activity and tyrosine titers during cockroach metamorphosis

Summary Tyrosine hydroxylation (TH) to dopa in vivo in nymphs and pharate adults ofPeriplaneta americana was very low, but increased over 30-fold beginning at ecdysis. Free tyrosine increased in pharate, adults and peaked at ecdysis, whereas TH activity peaked 6 h later. Both TH activity and tyrosine titers declined the next 24 h as the cuticle tanned. TH appears to regulate tanning substrate biosynthesis in cockroaches.Contribution No. 81-294-j, Department of Entomology, Kansas Agricultural Experiment Station, Manhattan KS. Research supported in part by National Science Foundation grant No. PCM-8003859. I wish to thank Dr. M.A.J. Al-Izzi for assistance with the enzyme analyses.