{"id":3985,"date":"2000-12-17T09:25:12","date_gmt":"2000-12-17T08:25:12","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=3985"},"modified":"2014-07-01T11:15:33","modified_gmt":"2014-07-01T11:15:33","slug":"zidovudine-didanosine-coexposure-potentiates-dna-incorporation-of-zidovudine-and-mutagenesis-in-human-cells","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/3985","title":{"rendered":"Zidovudine-didanosine coexposure potentiates DNA incorporation of zidovudine and mutagenesis in human cells"},"content":{"rendered":"<p><strong>Drug combinations that include nucleoside reverse transcriptase inhibitors (NRTIs) are remarkably effective in preventing maternal-viral transmission of HIV during pregnancy. However, there may be potential long-term risks for children exposed in utero.<\/strong><\/p>\n<p>Examination of the genotoxic and mutagenic effects of two NRTIs, zidovudine [AZT (3&#8242;-azido-3&#8242;-deoxythymidine)] and didanosine [ddI (2&#8242;,3&#8242;-dideoxyinosine)], in cultured human lymphoblastoid cells revealed multiplicative synergistic enhancement of AZT-DNA incorporation and mutant frequency induction in response to the combined drug exposure, as compared with single-drug exposures.<\/p>\n<p>Dose-related increases in DNA incorporation of AZT (as measured by a competitive RIA) and mutagenicity at the HPRT and TK loci (as assessed by cell-cloning assays) were observed in cells exposed in culture to AZT, or equimolar combinations of AZT + ddI, at exposure concentrations ranging from 3 to 30 times the maximum plasma levels found in humans.<\/p>\n<p>Because mutagenesis is strongly associated with tumor induction in experimental models, children exposed transplacentally to combinations of NRTIs may be at risk for cancer development later in life.<\/p>\n<p>Reference:<\/p>\n<p>Meng Q, Walker DM, Olivero OA et al, Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 23, 12667-12671, November 7, 2000<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Drug combinations that include nucleoside reverse transcriptase inhibitors (NRTIs) are remarkably effective in preventing maternal-viral transmission of HIV during pregnancy. However, there may be potential long-term risks for children exposed in utero. Examination of the genotoxic and mutagenic effects of &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[15],"tags":[],"class_list":["post-3985","post","type-post","status-publish","format-standard","hentry","category-basic-science-and-immunology"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/3985","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=3985"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/3985\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=3985"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=3985"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=3985"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}