The protective effect of thiola against the genotoxic action of benzo(a)pyrene

Summary The protective effect of Thiola against the genotoxicity, induced by benzo(a)pyrene, in vitro and in vivo, was investigated. By association of Thiola to benzo(a)pyrene a significant decrease of the numerical and structural chromosome aberrations and a reduction of the incidence of c-mitoses has been obtained in human diploid cells, i.e. human embryonic lung fibroblasts of the cell-line ICP-23, and C₅₆Bl/6 mouse bone marrow cells.     

Measurement of fluorescence decay of substances absorbed by an isolated living cell: an experimental device and early results]

A microfluorometric system allowing the mesurements of fluorescence decay (i.e. fluorescence lifetime) has been built. It will complete the microspectrofluorometric studies of absorbed compounds-polycyclic aromatic hydrocarbons, metabolites of benzo (a) pyrene-by single living cells and allows a better understanding of the intake and metabolisation of these compounds. The preliminary results with benzo (a) pyrene, dibenzocarbazole, pyrene are shown.     

Aryl hydrocarbon hydroxylase activity in type II alveolar lung cells

Summary Type II alveolar lung cells metabolize polycyclic aromatic hydrocarbons as indicated by measurements of aryl hydrocarbon hydroxylase activity and binding of tritium labeled benzo(a)pyrene to nuclear and cytoplasmic components.     

Effects of benzo(a)pyrene on isolated rat liver mitochondria

Riassunto Viene trattato mitocondri isolati di fegato di ratto con una soluzione acquosa di benzo(a)pyrene. I mitocondri cosi trattati appaiono rigonfi, hanno matrici chiare e notevole aumento degli spazi mannitolo-impermeabili. Queste modificazioni sono verosimilmente dovute all'azione del benzo(a)pyrene sulle molecole fosfolipidiche delle membrane motocondriali.     

Long-lasting persistence of elevated sister-chromatid exchange frequencies induced by perinatal benzo(a)pyrene treatment in rat bone-marrow cells

In this work the possibility that a mutagenic factor acting in utero or in the perinatal period might lead to elevated mutagenic rates in bone-marrow cells after a considerable period of time was examined. An aromatic hydrocarbon, benzo(a)pyrene was used as the test substance. Benzo(a)pyrene treatments resulted in significantly higher sister-chromatid exchange (SCE)-frequencies in both fetal and neonatal groups in both sexes, even four months after exposure. In a second experiment we examined whether mutagenic exposure suffered in utero could make the individual more susceptible to mutagenic effects in adulthood. Preliminary results indicate that such a possibility could exist.     

Direct fluorination of carcinogenic polycylic aromatic hydrocarbons. 6-Fluorobenzo(a)pyrene.

Xenon difluoride reacts with benzo[a]pyrene(BaP) in dichloromethane solution in an open system to give 6-fluorobenzo[a]pyrene. This method constitutes a direct route to fluorine substituted carcinogenic polycyclic aromatic hydrocarbons.     

Effets de la 2-mercaptopropionyl-glycine sur la différenciation de l'œuf d'oursin

Summary 2-Mercaptopropionyl-glycine (Thiola) exerted a strong animalizing action on the development of the sea urchin,Paracentrotus lividus. The action of Thiola on the synthesis of superficial and cortical cellular structures newly synthesized during the segmentation is suggested. These changes may alter the circulation of morphogenetic substances between blastomeres.     

Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems.

The covalent binding of tritiated benzo(a)pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP and DNA) and the biologically most relevant system (in vivo).     

Direct fluorination of carcinogenic polycyclic aromatic hydrocarbons. 6-Fluorobenzo[a]pyrene

Summary Xenon difluoride reacts with benzo[a]pyrene (BaP) in dichloromethane solution in an open system to give 6-fluorobenzo[a]pyrene. This method constitutes a direct route to fluorine substituted carcinogenic polycyclic aromatic hydrocarbons.Acknowledgment. This work was financed in part by a grant from The Israel Commission for Basic Research.     

Effects of polycyclic hydrocarbons on the induction of chromosomal aberrations in absence of an exogenous metabolic activation system in cultured hamster cells

Summary The effect of carcinogenic polycyclic hydrocarbons on the chromosomes of cultured Chinese hamster cells was investigated. Contrary to earlier reports it was observed that benz(a)anthracene, benzo(a)pyrene, 7, 12-dimethylbenz(a)anthracene and 3-methylcholanthrene were effective in causing chromosomal aberrations without any exogenous metabolic activation. Duration of incubation with these agents may be the cause of difference in results. Importance of prolonged treatment period is discussed.This study was supported by NIH-Minority Biomedical Support Program. Grant No. 5 RRO8124-05. Technical assistance of NIH-MBS students Rosetta Newsome and Samuel Loften is gratefully acknowledged.     

Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems

Summary The covalent binding of tritiated benzo(a) pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP with DNA) and the biologically most relevant system (in vivo).Presented in part at the 10th Annual Meeting of the Union of Swiss Societies of Experimental Biology, Experientia34, 925 (1978), abstract.Acknowledgment. We thank Dr G. Kistler, Institute of Anatomy, University of Zurich, for generously supplying the SIRC and VERO cell lines, and Mr P. Manser for the preparation of the granuloma pouch fibroblasts.     

Dietary carotenoids block photocarcinogenic enhancement by benzo (a)pyrene and inhibit its carcinogenesis in the dark

The carotenoids beta-carotene (C) and canthaxanthine (CX), with and without pro-vitamin A activity, respectively, when perorally administered to mice, markedly prevent benzo(a)pyrene photocarcinogenic enhancement (BP-PCE), continue to block such BP-PCE and protect significantly against BP carcinogenesis in mice maintained in the dark. These results appear relevant to both the pathogenesis of chemical carcinogenesis and rational programs of skin cancer prevention in humans.     

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.     

Effect of some derivatives of naphthalene on aryl hydrocarbon (Benzo[a]pyrene) hydroxylase in vitro

Résumé L'effet du naphthalène et certains de ses dérivés a été étudié in vitro sur l'action de l'aryl hydrocarbon (benzo[a]pyrene) hydroxylase. Les isomères naphthylphosphordicloridat-(1), naphthylphosphordicloridat-(2) et 2-methyl--naphtothioazol inhibent l'enzyme dans les microsomes des rats controles et des rats traités avec le méthylcholanthrène, sans un effet différentiel. Cette inhibition suggère l'occupation du site commun sur l'enzyme. Cependant le naphtalène, le naphthol-(1), le naphthol-(2) le naphthonitrile-(1), le naphthonitrile-(2) ont un effet negligeable sur l'activité enzymatique.     

Effect of benzo[a]pyrene on friend virus leukemogenesis,CFU-S viability,and induction of humoral immunity

Summary Benzo[a]pyrene (BP) potentiated the induction of leukemia by low doses of Friend virus in SJL/J mice if injected 2 days before the virus. BP also reduced the viability of hematopoietic stem cells (CFU-S) within this time interval but had little effect on the induction of humoral immunity (the PFC response).This work was supported by Department of Energy Contract No. EP-78-S-02-4800.     

Synthesis of ovulation-inhibiting compounds; structure-activity relationship.

We describe the synthesis of some new derivatives of benzo(4, 5)cyclohepta(1, 2-b)thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds.     

Synthesis of ovulation-inhibiting compounds; Structure-activity relationship

Summary We describe the synthesis of some new derivatives of benzo (4,5) cyclohepta (1,2-b) thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds.     

Die Wirkung von Benzpyren,Zigarettenrauchkondensat und passiver Berauchung auf die Bildung der Zoxazolaminhydroxylase

Summary Treatment with Benzo(a) pyrene, cigarette smoke condensate and cigarette smoke on hamsters and rats is able to induce zoxazolaminhydroxylase. Enzyme activity in hamsters is a priori higher, whereas the enzyme system in rats is of higher inducibility.     

Pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application

Human pluripotent stem cells [PSCs; including human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] can infinitely proliferate in vitro and are easily accessible for gene manipulation. Megakaryocytes (MKs) and platelets can be created from human ESCs and iPSCs in vitro and represent a potential source of blood cells for transfusion and a promising tool for studying the human thrombopoiesis. Moreover, disease-specific iPSCs are a powerful tool for elucidating the pathogenesis of hematological diseases and for drug screening. In that context, we and other groups have developed in vitro MK and platelet differentiation systems from human pluripotent stem cells (PSCs). Combining this co-culture system with a drug-inducible gene expression system enabled us to clarify the novel role played by c-MYC during human thrombopoiesis. In the next decade, technical advances (e.g., high-throughput genomic sequencing) will likely enable the identification of numerous gene mutations associated with abnormal thrombopoiesis. Combined with such technology, an in vitro system for differentiating human PSCs into MKs and platelets could provide a novel platform for studying human gene function associated with thrombopoiesis.     

Interaction of extrinsic fluorescent probes with E. coli glutamine synthetase.

Binding of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) to adenylylated (E--11) glutamine synthetase is cooperative and time-dependent, with 3 dye sites per subunit. In fluorescence polarization experiments TNS and pyrene butyrate give normalized Perrin plots that indicate a symmetrical arrangement of dye excited state dipoles, relative to the rotational axis of the oblate ellipsoid of the dodecameric native enzyme.