Cancer cells develop increased sensitivity to members of many virus families and, in particular, can be efficiently infected and lysed by many low-pathogenic human enteroviruses. However, because of their great genetic heterogeneity, cancer cells display different levels of sensitivity to particular enterovirus strains, which may substantially limit the chances of a positive clinical response. We show that a non-pathogenic strain of coxsackievirus B6 (LEV15) can efficiently replicate to high titers in the malignant human cell lines C33A, DU145, AsPC-1 and SK-Mel28, although it displays much lower replication efficiency in A431 and A549 cells and very limited replication ability in RD and MCF7 cells, as well as in the normal lung fibroblast cell line MRC-5 and the immortalized mammary epithelial cell line MCF10A. By serial passaging in RD, MCF7 and A431 cells, we obtained LEV15 strain variants that had acquired high replication capacity in the appropriate carcinoma cell lines without losing their high replication capability in the original set of cancer cell lines and had limited replication capability in untransformed cells. The strains demonstrated improved oncolytic properties in nude-mouse xenografts. We identified nucleotide changes responsible for the phenotypes and suggest a bioselection approach for a generation of oncolytic virus strains with a wider spectrum of affected tumors.
293 and RH cells derived from human embryo kidney were infected by Venezuelan equine encephalitis and tick-borne encephalitis viruses and cDNA libraries representing cellular mRNAs induced or suppressed due to the infection were prepared using suppressive subtractive hybridization. Among the up-regulated clones the RT-PCR and Northern analyses revealed an unusual transcript of the spermidine/spermine N1-acetyltransferase (SSAT) gene that was shown to be an alternatively spliced form containing an additional 110-bp exon. The alternatively spliced transcript is polyadenylated and can be expected to yield only a truncated 71 amino acid polypeptide. This first evidence of the host gene alternatively spliced mRNA induction by RNA viruses raises the questions of its biological role, regulation mechanisms of alternative splicing, and significance for the virus life cycle.
The effects of multiwalled carbon nanotubes on epitheliocytes of different compartments of the gastrointestinal tract and urothelium of different compartments of the renal nephron were studied in CBA mice. The nanotubes affected mouse gastrointestinal mucosa and renal urothelium. The cell reaction in the macula densa of the renal distal tubules and the immune system reaction to oral nanotubes were detected. A possible effect of nanotubes administered orally on the renal filtration function was hypothesized.
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