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PubMed1991

The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders.

Organic nitrates, cornerstones of antianginal therapy, are believed to exert their principal anti-ischemic benefit by relaxing vascular smooth muscle. Recent evidence suggests that these compounds and related nitro(so) vasodilators are also potent platelet inhibitors. In view of the well recognized role of thrombotic events mediated by platelets in acute coronary syndromes, the antiplatelet effect of nitrates may also be of mechanistic importance in the treatment of these disorders. This review details the biochemical mechanism by which nitro(so) compounds inhibit platelet function and summarizes the in vitro and in vivo evidence that supports their antithrombotic effects.

Angina, Unstable↗
PubMed1991

Expression of human O6-methylguanine-DNA methyltransferase in Chinese hamster ovary cells and restoration of cellular resistance to certain N-nitroso compounds.

We have constructed a plasmid in which the expression of human O6-methylguanine-DNA methyltransferase (MGMT) cDNA is driven by the Rous sarcoma virus promoter sequence. Transfection of this plasmid into Chinese hamster ovary (CHO) cells results in expression of MGMT and in cellular resistance to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 1-(2-chloroethyl)-1-nitrosourea (CNU), but not to N-nitroso-N-ethylurea. The specific activity of MGMT in transfected CHO cells correlated well with their resistance to MNNG and CNU. Southern analysis showed that the plasmid had been integrated into the CHO cell genome. Western analysis of extracts from transfected CHO cells using an antibody against a peptide corresponding to the carboxyl-terminal end of the human MGMT protein demonstrated a single band with a molecular size of 24-25 kDa; no such band was observed in extracts from wild-type CHO cells. These transfected cells may therefore be used to study the role of MGMT in the repair of alkylating DNA lesions and to determine its importance in carcinogenesis as well as in chemotherapy.

Alkylating Agents↗