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Biomedical subjects

H Lazarus

Publications and source records attributed to H Lazarus.

At least 91 records · Page 5Linked to original sources
PubMed1976

Accumulation of cystine auxotrophic thymocytes accompanying type C viral leukemogenesis in the mouse.

Certain continuous lymphoid and myeloid tumor cell lines of rodent origin are unable to grow in tissue culture in the absence of pre-formed L-cystine (CYS). In contrast, three NZB murine lymphoid cell lines obtained from NZB mice free of hematopoietic neoplasm can grow as well in cystine-deficient media containing L-cystathionine (CSN), the immediate precursor of CYS in the biosynthetic pathway, as in cystine sufficient medium. The former class of cells is, therefore, CYS auxotrophs (CYS-) and the latter CYS prototrophs (CYS+). Compared to CYS+ cells, the CYS- lines appear to be relatively deficient in the enzyme cystathionase, which catalyzes the cleavage of CSN to CYS and alpha-ketobutyrate. Using protein synthetic capacity as a criterion, normal thymocytes from mixed-bred Swiss mice behave like CYS prototrophs, while those from littermates bearing Moloney type C virus-induced thymic tumors behave like CYS auxotrophs. The former are also characterized by substantially higher levels of cystathionase than the latter. Extracts of thymocytes from tumor-free AKR mouse thymus are also characterized by higher levels of cystathionase activity than extracts of spontaneous AKR thymomas. Exogenous in vitro type C virus infection of a CYS+ cell results in vigorous virus production but no concomitant reduction in cystathionase activity. Thus viral replication alone in any random lymphoid cell is not sufficient to alter the enzyme level. The data therefore suggests that CYS auxotrophy may closely accompany neoplastic transformation of certain hematopoietic cells in vivo, including that induced by certain "thymic" type C viruses.

Animals↗
PubMed1976

Nucleosides. 1. 9-(3'-Alkyl-3'-deoxy-beta-D-ribofuranosyl)adenines as lipophilic analogues of cordycepin. Synthesis and preliminary biological studies.

A series of lipophilic 9-(3'-alkyl-3'-deoxy-beta-D-ribofuranosyl)adenines of increasing chain length was synthesized from the corresponding branched sugars via titanium chloride catalyzed ribosylation of chloromercuri-6-benzamidopurine. Enhanced growth inhibitory activity was observed against (CCRF-CEM human lymphoblastic leukemia cells in culture as the length of the alkyl side chain in the sugar and the resultant lipophilic character of the nucleoside were increased. Experiments involving incorporation of radiolabeled uridine, thymidine, and leucine revealed that in contrast to cordycepin (1) the 3'-n-butyl and 3'-n-hexyl analogues 5 and 6 markedly inhibit not only RNA synthesis but DNA and protein synthesis as well.

Animals↗
PubMed1975

7-substituted actinomycin D analogs. Chemical and growth-inhibitory studies.

The synthesis and biological activity of three 7-substituted actinomycin D derivatives are reported. Three such derivatives, 7-nitro-, 7-amino-, and 7-hydroxyactinomycin D, were synthesized via new methods which were first tested successfully with a chromophore model system. Of these, 7-nitro- and 7-aminoactinomycin D were assayed for growth inhibitory activity against mammalian cells (CCRF-CEM human lymphoblastic leukemia) in vitro and against the Ridgway osteogenic sarcoma and the L1210, P1534, and P388 murine leukemias in vivo. In these systems, the inhibitory activity of the 7-substituted analogs was comparable to actinomycin D. In two bacterial systems ( (L. casei and L. arabinosus) in vitro, on the other hand, these compounds showed inhibitory profiles which are distinctly different from actinomycin D. These studies demonstrate that substitution at the 7 position, which does not interfere with DNA binding, is capable of yielding experimental antitumor agents with significant activity against a variety of tumors.

Animals↗
PubMed1970

Growth characteristics of virus-transformed cells. Maximum population density, inhibition by normal cells, serum requirement, growth in soft agar, and xenogeneic transplantability.

Virus transformants (like cancer cells, cells transformed by X-ray or carcinogens, or those which have transformed spontaneously) exhibit a number of phenotypic changes which are usually associated, and which may be lost concurrently. That association is, however, not invariable. More particularly, the altered characteristics here studied (escape from contact inhibition of growth and susceptibility to inhibition by other cells, decreased serum requirement, and ability to grow in soft agar) do not, in and of themselves, endow the cell with the capacity to produce a tumor, at least as judged by the methods of assay here used. Although the question as to whether the tumorigenicity of virus transformants is causally linked to any of these associated changes cannot be answered definitively, the evidence suggests a close linkage, rather than identity, between the determinants of oncogenicity and the other properties here studied.

Adenoviridae↗