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Showing papers in "Chemico-Biological Interactions in 1988"


Journal ArticleDOI
TL;DR: While oxidative processes may cause toxicity, the arylation of intracellular thiols or nucleophiles also contributes significantly to the cytotoxicity of compounds such as menadione.

289 citations


Journal ArticleDOI
TL;DR: Glutathione appears to be an intrinsic protector against cadmium toxicity, while MTs serve as an induced cellular defense that is mobilized against heavy metal stress, but takes more than 2 h to accumulate in significant amounts.

134 citations


Journal ArticleDOI
TL;DR: The data presented suggest that ethanol-derived radicals could be generated during the microsomal metabolism of alcohol probably through two different pathways and might be relevant in understanding the pathogenesis of the liver lesions which are a consequence of alcohol abuse.

125 citations


Journal ArticleDOI
TL;DR: The cytotoxicities of a linoleic acid hydroperoxide and its related aldehydes were found to be much reduced in growth medium containing serum, growth factors, heparin, amino acids and vitamins.

98 citations


Journal ArticleDOI
TL;DR: Observations indicate that this enzyme may actually be localized in peroxisomes in vivo and is recovered in the high-speed supernatant because of fragmentation of these fragile organelles during homogenization, and the functional significance of cytosolic epoxide hydrolase is still largely unknown.

97 citations


Journal ArticleDOI
TL;DR: 3-MeSO2-DDE is a persistent environmental pollutant with a unique ability to produce acute toxicity subsequent to metabolic activation in a mammalian tissue and to cause acute toxicity after single doses down to 25 mg/kg.

89 citations


Journal ArticleDOI
TL;DR: Data support the hypothesis that plasma retinol reduction by TCB might result from a weakening of the RBP-TTR complex, in the presence of the TCB metabolite bound to the TTR.

82 citations


Journal ArticleDOI
TL;DR: The cancer chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-DDP) produces bifunctional reactions with DNA which appear critical to its toxic action and these reactions have been characterized by platinating pure DNA followed by enzyme digestion, HPLC separation and analysis by atomic absorption and nuclear magnetic resonance (NMR).

72 citations


Journal ArticleDOI
TL;DR: The method applied in this study allows the analysis of DNA damage and the identification or exclusion of the participation of different ultimate reactive species without chemical identification of the lesions.

70 citations


Journal ArticleDOI
TL;DR: The results indicate that simply depleting GSH prior to DDP exposure is not sufficient for sensitizing these cells to D DP, and exposure to GSH depletion must be maintained during DDP treatment for enhancement of DDP cytotoxicity to occur.

70 citations


Journal ArticleDOI
TL;DR: The pro-oxidant character of the reductive addition of GSH to p-benzoquinones, alpha-hydroxyquinones and quinone epoxides is discussed in terms of the pro-oxygen character of this compound.

Journal ArticleDOI
TL;DR: A mechanism for the hydrolytic deamination of 3- HP-dCyd to 3-HP-dUrd involving the OH on the HP side chain is proposed and may play a role in the mutagenic and carcinogenic activity of this epoxide.

Journal ArticleDOI
TL;DR: Monitoring MDA excretion in urine can give useful information about lipid peroxidation in vivo, and the peak urinary concentration approached the expected plasma concentration and reproducible recovery data were obtained, suggesting that MDA was passively excreted in a reasonably stable form.

Journal ArticleDOI
TL;DR: It is shown that relatively low concentrations of APAP stimulate PGHS activity in ram seminal vesicle microsomes, whereas high concentrations inhibit the conversion of arachidonic acid to 15-hydroperoxy-9,11-peroxidoprosta-5,13-dienoic acid (PGG2).

Journal ArticleDOI
TL;DR: The results obtained suggest that the formation of a thioacylating intermediate (a thioketene or a thiono acyl chloride) may be the decisive reaction during the beta-lyase dependent activation of PCBC.

Journal ArticleDOI
TL;DR: Lipoperoxidative damage caused by exposure of isolated hepatocytes or cultivated hepatoma cells to ADP-iron or to 4-hydroxynonenal induces the synthesis of some proteins which are different under these two conditions but are always a subset of the proteins induced in each type of cells upon heat-shock (heat-shock proteins).


Journal ArticleDOI
TL;DR: Experiments on the influence of different cytochrome P-450 inducing agents on the ratio of drug bound to hemoglobin versus hepatic proteins suggested that the reactive metabolites of APAP are formed in the liver and migrate to the erythrocyte, rather than being produced by hemoglobin-catalyzed oxidation of AP AP.

Journal ArticleDOI
TL;DR: Results indicate that the structure of the substituent on the sulfur atom is an important determinant for the biological activity of cysteine S-conjugates.

Journal ArticleDOI
TL;DR: In agreement with a 2-electron oxidation hypothesis, iodosobenzene-dependent oxidation of PAR by cyt.

Journal ArticleDOI
TL;DR: Roxithromycin and its metabolite RU 39001 exhibit a very poor affinity for rat liver cytochrome P-450, an unability to be metabolized into a stable inhibitory metabolite-cytochromeP-450 complex and a decreased ability to induce liver cy tochrome P -450 PCNE, an isozyme implicated in drug associations involving some macrolide antibiotics.

Journal ArticleDOI
TL;DR: In microsomal incubations as well as in a reconstituted system containing purified cytochrome P-450b, 1,4-TCHQ oxidation and subsequent protein binding was shown to be completely dependent on NADPH.

Journal ArticleDOI
TL;DR: The results suggest that the phenoxyacid herbicides act as mixed inducers of the cy tochrome P-450 mixed function oxidase system, preferentially inducing the cytochrome V-450 IVA1 isoenzyme.

Journal ArticleDOI
TL;DR: The autoxidation of N,N,N',N'-tetramethyl-p-phenylenediamine at neutral pH has been shown to generate superoxide radical and hydrogen peroxide and it is suggested that 'active oxygen' species may be involved in the initiation of these harmful effects.

Journal ArticleDOI
TL;DR: Data support the conclusion that ABS has a functional role in the anti-proliferative effect of triphenylethylene anti-estrogens and structurally related compounds.

Journal ArticleDOI
TL;DR: The mechanism of cocaine-induced cytotoxicity was investigated in hepatocytes isolated from both male C3H mice and male Sprague-Dawley rats and data suggest that neither generalized protein thiol depletion nor lipid peroxidation are critical determinants of cocaine's cytotoxic effects in cellular systems.

Journal ArticleDOI
TL;DR: The results suggest that the processes of peroxisome proliferation and induction of cytosolic epoxide hydrolase are intimately related.

Journal ArticleDOI
TL;DR: The ring-opening and depurination of the alpha- and beta-isomers corresponded to their respective pK alpha values and the 7-alkyldeoxyguanosine derivatives of styrene oxide depurinated equally fast as 7-methyldeoxy guanosine, by contrast, the depurinations of 7-alkylguanine was 15 times slower in the single-stranded DNA and 55 times slowerIn the double-Stranded DNA.

Journal ArticleDOI
TL;DR: N-nitrosodimethylamine N-demethylase activity, DNA alkylation, capacity for O6-methylguanine repair and cell proliferation, and de novo liver DNA synthesis were measured in livers of newborn and adult CFW mice after a single carcinogenic dose of DMNA.

Journal ArticleDOI
TL;DR: The absence of an organic anion transporter limits the usefulness of LLC-PK1 cells for the study of nephrotoxicity of compounds needing this transport to enter the cells, but the finding of an active basolateral organic cation transporter, together with the presence of gamma GT, dipeptidase and beta-lyase, makes this system especially interesting for testing all compounds that use this transporter or these enzymes in order to elicit toxicity.