当前位置： SCI文献检索 > MOLECULAR AND BIOCHEMICAL PARASITOLOGY期刊下所有文献 > Reduced purine accumulation is encoded on an amplified DNA in Leishmania mexicana amazonensis resistant to toxic nucleosides.

Reduced purine accumulation is encoded on an amplified DNA in Leishmania mexicana amazonensis resistant to toxic nucleosides.

Abstract：

:Nucleoside analogs are potential anti-Leishmania agents. To better understand how these compounds might lose their effectiveness, Leishmania were independently selected for resistance to inosine dialdehyde or tubercidin. Each of the resistant cells exhibited resistance to inosine dialdehyde and tubercidin as well as to formycin B and allopurinol ribonucleoside. Resistant cells had a greatly reduced capability of accumulating exogenous adenosine, guanosine, thymidine and guanine. This decreased ability to accumulate nucleosides and at least one nucleobase appeared to be due to reduced activity of a number of distinct purine transporters, as the differences between purine metabolizing enzymes were not sufficiently different to account for the decreased accumulation capability. The resistance to toxic nucleosides and the decreased ability to accumulate purines were due to the presence in the resistant cells of an extrachromosomal DNA approximately 55 kb in size. The extrachromosomal DNA was not detected in wild-type cells or revertants which have lost resistance to toxic nucleosides. Except for a 1.2-kb difference, the extrachromosomal DNA from both independently selected resistant cells appeared to be identical. The resistant cells contained 2-4 times as much DNA homologous to the extrachromosomal DNA as compared to wild type cells. When cloned into an E. coli/Leishmania shuttle vector, a portion of the amplified DNA had the ability to confer upon wild-type cells resistance to the toxic purine nucleoside analogs tubercidin and inosine dialdehyde. These transformed cells also exhibited a decreased ability to accumulate non-toxic purine nucleosides.

journal_name

Mol Biochem Parasitol

journal_title

Molecular and biochemical parasitology

authors

Kerby BR,Detke S

doi

10.1016/0166-6851(93)90129-l

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

171-85

issue

2

eissn

0166-6851

issn

1872-9428

pii

0166-6851(93)90129-L

journal_volume

60

pub_type

杂志文章

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