کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2603857 1133840 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Down-regulation of gene transcripts associated with ricin tolerance in human RPMI 2650 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Down-regulation of gene transcripts associated with ricin tolerance in human RPMI 2650 cells
چکیده انگلیسی

The present study sought to determine if novel therapeutic approaches against ricin intoxication could be identified from human respiratory tract cells selected for increased resistance to this toxin. Initial studies indicated that the RPMI 2650 line was an appropriate model, owing to its sensitivity to ricin. Tolerant cultures were developed by exposing cells to a graded series of ricin concentrations from 6 to 192 pM. This resulted in the generation of cultures whose LC50 values were increased by up to 4-fold following exposure to up to 96 pM ricin and by up to 6-fold following exposure to up to 192 pM ricin, compared to control cultures. DNA microarrays were employed to determine the gene transcript expression profile of cultures with increased resistance to ricin to investigate which gene products mediate ricin resistance. Transcripts (10) were identified that were greater than 2-fold down-regulated in the cells tolerant to 96 pM ricin, whereas 48 transcripts were seen to be down-regulated in cultures tolerant to 192 pM ricin. Gene transcripts (5) were up-regulated 2-fold or more in the 192 pM tolerant cultures in comparison to unexposed cells. The results indicate that ricin tolerance is the product of complex changes in gene expression profiles, most of which were found to involve down-regulation of transcript expression. It may be possible to modulate the gene expression profiles associated with ricin tolerance for potential therapeutic purposes using drugs and antisense technologies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 21, Issue 3, April 2007, Pages 509–520
نویسندگان
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