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C J Larsen

Publications and source records attributed to C J Larsen.

161 records · Page 9Linked to original sources
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Effects of BD-40, an ellipticine analogue (aza-ellipticine) on cell cycle traverse and DNA synthesis in cultures of synchronized mouse fibroblasts.

BD-40 is a pyrido-pyrrolo-isoquinoline analogue of ellipticine, which possesses oncostatic in vivo activity on experimental tumors, and dose-dependent cytostatic and cytotoxic activities on mammalian cells in culture. In order to appreciate the effects of the drug on the replication of DNA, cultures of murine fibroblasts were synchronized by thymidine double block, and BD-40 was added at the time of the block release. The drug did not interfere with the entry of cells in S phase, but a delay in S-phase transit was observed, regardless of the dose employed. In agreement with these data, DNA synthesis started at the same time in control cells and in BD-40 treated cells, but a significant reduction of 3H thymidine incorporation was found in drug-treated cells. This inhibition was not likely to result from a diminution of the specific activity of 3H-dTTP, since nuclei, isolated from cells previously incubated with the drug, also presented a strong diminution of synthetic activity in the presence of the four nucleoside triphosphate precursors (dNTPs). Analysis by alkaline sucrose gradient centrifugation of DNA synthesized in the presence of BD-40 showed that primary fragments, probably corresponding to the duplication of initial replicons, were normally formed but were not further elongated in cells treated with cytotoxic doses, while they were normally processed (although at a slower rate than in control) with a cytostatic drug concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Isolation and characterization of a gp 70+ non producer Friend tumor cell clone.

Viral expression was analyzed in ten cell clones of a Friend erythroleukemia cell line (HFL/b cell line [3]), which had lost its capacity to produce infectious particles. All the ten subclones were non producers but expressed spleen focus forming virus (SFFV) polypeptides in the form of p48-p50gag and gp50-gp52env. One subclone (subclone 9) expressed the gp70env of the Friend-MuLV helper component of the Friend virus complex. Comparative analysis of viral RNA expression in one gp70- subclone (subclone 2) and in the gp70+ subclone (subclone 9) was performed using specific ecotropic env gene probe and MCF/xenotropic env gene probe. In both subclones 2 and 9, the MCF/xenotropic env gene probe detected 32S SFFV genomic RNA, 20S SFFV env gene mRNA and a 34S RNA. The ecotropic env probe failed to characterize any 38S F-MuLV genomic RNA in both clones but detected 34S RNA and 24S env mRNA in the gp70+ subclone 9. These data show that expression of a complete F-MuLV genome is not required for synthesis of env gene products.

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[Application of technics for the hybridization between nucleic acids in Oncornavirus research].

The RNA-dependent DNA polymerase of oncornaviruses is a very useful tool for synthesizing DNAs complementary to the viral genomes. These probes have been successfully utilized during the last years to detect viral sequences in the DNA or RNA of virus producing or non-producing cells. The results obtained at the present time lead to a better understanding of the molecular events of virus replication and transformation by oncornaviruses. The same approach has been used to look for the presence of virus-like nucleotide sequences in various human cancers. Although promising results have been obtained, they do not establish that oncornaviruses are directly implicated in etiology of human cancers.

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