The structure of PB-1, an unusual toxin isolated from the red tide dinoflagellate Ptychodiscus brevis.

The structure of PB-1, an unusual toxin isolated from the red tide dinoflagellate Ptychodiscus brevis.

AMSrwn, P. A., Wwrra, T. V. and Cnaatrrn, P. A. (Department of Cardnogenesis, Swiss Institute for Experimental Cancer Research, CH-1066 fipalingea s/L...

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AMSrwn, P. A., Wwrra, T. V. and Cnaatrrn, P. A. (Department of Cardnogenesis, Swiss Institute for Experimental Cancer Research, CH-1066 fipalingea s/Lsusanne, Switzerland) Removal of aflatoxin B-DNA adducts and in vitro transformation in mouse embryo fibroblasts C3H/lOTih . J. nota. Cancer last. 70, 133 (1983) . Ttm na:ct~uw~snf of in vitro transformation of the mouse embryo flbroblast C3H/IOTA clone 8 by aflatoxin B, (AFB was studied in confluent holding (CH) experiments . Confluent cultures of C3H/IOT~ cellswere treated with AFB, for 16 hr and the DNA adduct composition and concentration were determined by chromatographic procedures after 0, 8, 16 and 40 hr of CH, when the cells were replaced at low density for the expression of their colony-forming ability and the formation of transformed fod. Total adduct concentration and the concentration of the major primary adduct 2,3-dihydro-2-(N'-guanyl}3-hydroxyaflatoxin B, (AFB,-N'-Gua) decreased continuously during CH due to spontaneous decomposition and probably also due to enzymatic rrpair processes. In contrast, the more chemically stable secondary product 2,3-dihydro-2(N'-formyl-2',S',6'triamino-4'-oxo-N'-pyrimidyl}3-hydroxyaflatoxin B, (AFB,-triamino-Py) accumulated in the DNA and reached its maximum concentration after 16 hr of CH . While the loss of total AFB,-DNA adducts during CH was reflected in recovery of viability, the potential to form transformed foci reached a maximum after 16 hr of CH and then decreased with continued CH, below the initial value. Therefore, no simple relationship exists between the concentration of the total adducts AFB,-N'-Gua and AFB,-triamino-Py at the time of release from CH and the potential to form transformed foci . However, DNA lesions or abnormal DNA configurations formed during CH as a rnnsequence of the cellular processing of AFB, - DNA adducts may play a role in the transformation process. ttiuwor's uoeua.y H.P . Kot.M PEnRCe, B. R., G~rtn, A. L. and Dtm'orr, G. R. (Department of Pharmacology, College of Medidne, University of Iowa, Iowa City, Iowa, U.S .A .) Tetanus toxin inhibition of K'-stimulated ['HIGABA release from developing cell cultures of the rat cerebellum . J. Nererochem. 40, 887 (1983) . TttE effect of tetanus toxin pretreatment on K*-stimulated fH]r-aminobutyric acid release from neuronenriched cerebellar all cultures at various stages during their development in vitro was assessed . Tetanus toxin had little inhibitory effect on immature (1-3 day-old) cultures, but markedly reduced K*-evoked ('Hlyaminobutyric acid release from 7- and 14-day-old cultures (N80~1o inhibition). It is suggested that cerebellar neurons in culture develop tetanus toxin-sensitive transmitter release mechanisms similar to their in vivo counterparts . (Author's abstract) H. P. KOLM DrNovr, M., TRAINOR, D. A., NAICANISHI, K., S~wou~n, R. and At.,ut, M. (Department of Chemistry, C~nlnmhia University, New York, NY 10027, and Department of Medidnal Chemistry, University of Houston, TX 77004, U.S .A .) The structure of PB-1, an unusual toxin isolated from the red tide dinoflagellate Ptychodisrus brevis. Tetrahedron Lett. 24, 833 (1983) . Tie tctrrrtvo~roxw PB-1 was isolated from cultured Ptychodisrus brevis . Its structure was determined to be O,O~iphenyl-N~yclooctyl phoaphoramidate. H. P. KOLM Hues, M., Tu, A. T. and Et.-Assutt, F. (Department of Biochemistry, Colorado State University, Fort Collies, CO 80323, U.S .A ., and Department of Biochemistry, Ain Shams University, Faculty of Medicine, Cairo, Egypt) Isolation of minax toxins from the venom of the scorpion Buthus mirtax and their metabolic effects . Archs Biochem. Biophys. 220, (1983) . Two rr8uao~roxtrvs, minax toxins 1 and 2, were isolated from venom of the scorpion Buthus minor from the Sudan. Molecular weights of 7000 and 6800 and 66 and 62 amino adds were found for minax toxins 1 and 2, respectively. Both toxins contain four disulfïde bonds, 1 mole each of phenylalanine, histidine and tryptophan, no fra aulfhydryl groups and no methionine. Hoth minax toxins 1 and 2 are basic polypeptides with iaoelectric points of 8.2 and 9.0, respectively . There is a significant increase in the caldum content of rat hearts envenomated with minax toxins 1 and 2 or crude venom. This confirms earlier electron microscopic fmdinga of caldum deposits in the heart following scorpion envenomation . There is a concomitant decrease in the caldum and phosphorus content of rat serum following envenomation . It seems that neither scorpion toxins nor scorpion vmoms affect the mineral metabolism of the bone. The present investigation indicates that scorpion toxins have not only a neurotoxic acdon, but also broader biological effects, such as on mineral metabolism. (Author's abstract) H. P. Kot.nt