Dehydroretronecine, an antimitotic and carcinogenic agent, reacted with deoxyguanosine at pH 7.4 in vitro to yield in nearly equal quantities two major adducts, which were isolated by thin-layer and high-pressure liquid chromatography. The adducts were stable at pH 8.7 and 30°for at least 24 hr, showed pK.s at acidic and alkaline pHs, reacted with 4-(p-nitrobenzyl)pyridine, had a nonexchangeab...

Benzo(a)pyrene (BaP) is highly carcinogenic in rats but is without effect in rabbits when administered s.c. The possibility that BaP-DNA adducts could be responsible for this species difference was investigated by comparing BaP-deoxyribonucleoside adducts formed in dermal fibroblast cultures from Wistar rats and New Zealand rabbits. Treatment with [G-3H]BaP (1.2 microM) for 6, 24, and 48 h prod...

The site of DNA interstrand cross-linking identified by a family of pyrrole-derived bifunctional electrophiles was studied in vitro in synthetic DNA duplexes. This family includes reductively activated mitomycin C (l), oxidatively activated pyrrolizidine alkaloids (e.g. 2), the simple pyrroles 2,3and 3,4-bis-(acetoxymethyl)1-methylpyrrole (3 and 4), and the antitumor substance 2,3-dihydro-5-(3’...

Conformational possibilities of a series of deoxyguanosine analogues possessing or lacking antiviral activity were evaluated using methods of the molecular mechanics. Comparison of the spatial structures of acyclic analogues with one another and with the spatial structures of deoxyguanosine demonstrates restricted conformational mobility for compounds devoid of activity. The level of sterically...

Cultured malignant human lymphocytes are highly sensitive to growth inhibition by thymidine (50% inhibitory dose congruent to 10(-5) M). Growth inhibition reflects sustained elevation of the deoxythymidine 5'-triphosphate pool associated with secondary elevation of the deoxyguanosine 5'-triphosphate pool and reduction in the deoxycytidine 5'-triphosphate (dCTP) pool. Deoxycytidine was capable o...

Purine nucleoside phosphorylase (PNP) deficiency is associated with a severe defect in thymus-derived (T)-lymphocyte function combined with normal bone marrow-derived (B)-lymphocyte function. To investigate the role of this enzyme deficiency in the resulting immune dysfunction, we measured the levels of ribonucleoside and deoxyribonucleoside triphosphates in erythrocytes from two unrelated PNP-...

DNA is subject to constant oxidative damage from endogenous oxidants. The oxidized DNA is continuously repaired and the oxidized bases are excreted in the urine. A simple routine analytical procedure is described for urinary 8-hydroxy-2'-deoxyguanosine, an oxidative DNA damage adduct, as an indicator of oxidative damage in humans and rodents. This adduct was purified from human urine and charac...

Purine riboswitches have an essential role in genetic regulation of bacterial metabolism. This family includes the 2'-deoxyguanosine (dG) riboswitch, which is involved in feedback control of deoxyguanosine biosynthesis. To understand the principles that define dG selectivity, we determined crystal structures of the natural Mesoplasma florum riboswitch bound to cognate dG as well as to noncognat...

Oxidative stress, which is characterized by disruption of the oxidant/antioxidant balance, causes pathological processes, including toxicities induced certain mycotoxins. The present study was designed to investigate effects resveratrol on sirtuin deacetylases (SIRT2 and SIRT3), nitric oxide (NO), reduced glutathione (GSH) malondialdehyde (MDA) in fumonisin B1-induced hepatotoxicity. Regarding ...