Abstract：
:This study examines the relationship between cell progress into the state of unbalanced growth, hydrolytic enzyme activities and cell survival during the exposure of L5178Y cells to hydroxyurea (HU), excess thymidine (dThR), hydroxyurea with excess of four deoxyribonucleosides (dNR) or excess dTHR with deoxycytidine (dCR). Cell progress into the state of unbalanced growth was measured as cell size, protein/DNA ratio and protein content per cell. Activities of two lysosomal (acid phosphatase, beta-N-acetylglucosaminidase) and one cytoplasmic non-lysosomal (LDH) enzymes were determined. It has been found that in cells arrested by HU or excess dThR, a progressive cell volume increase with protein/DNA imbalance is correlated with a progressive increase in lysosomal and non-lysosomal hydrolase activities in the cells and in the medium and with a marked lethal effect. Cell volume increase, enhancement of enzyme activities and cell killing could be prevented in HU-arrested cells by concomitant addition of excess dNR (deoxyadenosine, deoxyguanosine, thymidine, deoxycytidine) leading to equal inhibition of DNA and protein synthesis. Control-like values of all parameters were achieved also in cells in which the dThR-inhibiting effect was reversed by dCR addition. It is suggested that a common pathway in the mode of action of the chemotherapeutic agents inducing cell killing through the state of unbalanced growth can be the over-production, abnormal accumulation and progressive leakage of numerous hydrolytic enzymes through the cell membranes, leading in consequence to 'lytic' cell death.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Malec J,Przybyszewski WM,Grabarczyk M,Sitarska E,Czartoryska Bdoi
10.1016/0009-2797(86)90006-2subject
Has Abstractpub_date
1986-03-01 00:00:00pages
315-24issue
3eissn
0009-2797issn
1872-7786pii
0009-2797(86)90006-2journal_volume
57pub_type
杂志文章abstract：:A chromatographic procedure for improved separation of deoxyribonucleosides and methylated deoxyribonucleosides is described. DNA was isolated from liver and small intestine of rats treated with [14C]dimethylnitrosamine ([14C]DMN) or N-[3H]methyl-N-nitrosourea ([3H]MNU), and the purified DNA was hydrolyzed enzymatical...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(77)90123-5
更新日期：1977-02-01 00:00:00
abstract：:The hydrolysis of paraoxon (POX), phenylacetate (PA) and beta-naphthylacetate (BNA) was studied in human serum. Based upon correlations between enzyme activities, upon reversible inhibition by EDTA and upon progressive inhibition by iso-OMPA, tabun, eserine and bis-4 nitrophenylphosphate, the following conclusions wer...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(93)90027-v
更新日期：1993-06-01 00:00:00
abstract：:DNA-protein cross-links were detected in several types of mammalian cells in culture when they were exposed to chromate salts. The cell types included human bronchial epithelial cells--the apparent cell type of origin of the malignancies reported in chromate workers. The level of cross-linking was proportional to the ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90077-6
更新日期：1981-09-01 00:00:00
abstract：:Fatty liver is the earliest and most common response of the liver to consumption of excessive alcohol. Steatosis can predispose the fatty liver to develop progressive liver damage. Chief among the many mechanisms involved in development of hepatic steatosis is dysregulation of insulin-mediated adipose tissue metabolis...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109059
更新日期：2020-05-01 00:00:00
abstract：:Oxidative stress can induce complex alterations of membrane proteins in red blood cells (RBCs) eventually leading to hemolysis. RBCs represent a good model to investigate the damage induced by oxidizing agents. Literature data have reported that chalcogen compounds can present pro-oxidant properties with potent inhibi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.10.007
更新日期：2009-01-15 00:00:00
abstract：:Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower Km value toward tiaprofenic acid than the cytoso...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.03.006
更新日期：2017-10-01 00:00:00
abstract：:Known spectroscopic and kinetic data are used to formulate pathways of the physiological and transfer reactions and the substrate inhibition of phenol sulfotransferase. Kinetic mechanisms indicate that release of PAP from enzyme complex is required for the physiological reaction but not for the transfer reaction. The ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00127-0
更新日期：1998-02-20 00:00:00
abstract：:Unscheduled DNA synthesis (UDS), following exposure to dimethylnitrosamine (DMN), was potentiated in cultured hepatocytes isolated following treatment of rats for 14 or 28 days with 20% ethanol/5% sucrose solution. Ethanol treatment was associated with increased UDS, a concomitant increase in hepatic microsomal protei...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(84)90039-5
更新日期：1984-08-01 00:00:00
abstract：:The extent of DNA modification in cancerous rat live and lung tissues was investigated and compared to their respective normal tissues. Liver tumors were induced by 2-fluorenylacetamide (2-FAA) or N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA), and lung tumors were induced by sodium nitrite plus trimethylamine. In the ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(94)03327-5
更新日期：1995-02-01 00:00:00
abstract：:The effects of pH on access to the cytochrome P-450 active site, N-demethylation and formation of the cytochrome P-450 Fe(II)-RNO metabolite complex for a series of erythromycin derivatives were examined. Studies were performed with dexamethasone-treated rat liver microsomes containing large amounts of cytochrome P-45...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90063-q
更新日期：1992-12-01 00:00:00
abstract：:Benzene exposure in occupational settings often occurs with concurrent exposure to toluene, the methyl-substituted derivative of benzene. Toluene is also readily metabolized by CYP450 isozymes although oxidation primarily occurs in the methyl group. While earlier mouse studies addressing co-exposure to benzene and tol...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.01.012
更新日期：2010-03-19 00:00:00
abstract：:Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, which plays an important role on mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve Ca(2+)i handling in hypoxic myocardial injury. Cardiomyocytes isolated from neonat...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.04.022
更新日期：2015-07-05 00:00:00
abstract：:The mechanisms by which soybean- and soybean isoflavone-enriched diets inhibit carcinogenesis are not known. We found that the isoflavones genistin and daidzin, and their respective aglucone forms daidzein and genistein, block 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin)-induced CYP1A1 enzyme activity. This inhi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00121-0
更新日期：1999-11-15 00:00:00
abstract：:Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) reduces tissue injury associated with inflammation in vivo by mechanisms that are not completely understood. Here we evaluate...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109210
更新日期：2020-09-25 00:00:00
abstract：:Previous studies revealed that direct contact with graphene oxide (GO) induced cytotoxic effects, but the importance of involvement of metabolic pathways, in particular lipid metabolism pathways, might be overlooked. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to GO with large size (den...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109325
更新日期：2021-01-05 00:00:00
abstract：:4-methylesculetin (4 ME) is a natural antioxidant coumarin with protective effects on the intestinal inflammation, in which oxidative stress plays a key role in its aetiology and pathophysiology. Based on this, we examined the antioxidant molecular mechanisms involved in the intestinal anti-inflammatory activity of th...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.108876
更新日期：2020-01-05 00:00:00
abstract：:The relationship between dimethylnitrosamine (DMN) demethylase activity and DMN-induced mutagenesis was investigated in Drosophila melanogaster. The activity of DMN-demethylase was at least 10-fold greater in the Hikone-R strain than in three other Drosophila strains. However, the sex-linked recessive lethal (SLRL) mu...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(83)90006-6
更新日期：1983-08-15 00:00:00
abstract：:Monomeric carbonyl reductase 1 (CBR1, SDR21C1) is a member of the short-chain dehydrogenase/reductase superfamily and is involved in the metabolism of anthracycline anti-cancer drugs, prostaglandins, and isatin, which is an endogenous inhibitor of monoamine oxidases. Additionally, cancer progression may be partly regu...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.11.023
更新日期：2013-02-25 00:00:00
abstract：:Two homogenous fractions of hepatic metallothioneins ((Cd,Zn) MT-1 and (Cd,Zn) MT-2) and renal metal binding proteins ((Bi,Cu) BP-1 and (Bi,Cu) BP-2) were isolated from rats exposed to heavy metals and specific antisera to them were produced in rabbits. These antisera were tested by immunodiffusion and immunoelectroph...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90048-4
更新日期：1980-12-01 00:00:00
abstract：:The effects of norharman (NH) on the metabolism of dibenzo[a,e]-fluoranthene (DBF) and on its fixation on DNA, RNA and proteins have been studied in vitro by incubation with S-9 and microsomes from rats and mice. NH causes a decrease of the activity of microsome monooxygenases proportionally to its concentration but h...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90169-1
更新日期：1981-10-01 00:00:00
abstract：BACKGROUND:Mild hyperhomocysteinemia is associated with premature vascular disease. The mechanism behind the vascular injuries is, however, still unknown. Homocysteine may be catabolized in the trans-sulfuration pathway to cysteine. Cystathionine beta-synthase, which catalyses the first step in the trans-sulfuration pa...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2006.10.009
更新日期：2007-01-05 00:00:00
abstract：:Organophosphorus compounds have been widely employed to the development of warfare nerve agents and pesticides, resulting in a huge number of people intoxicated annually, being a serious problem of public health. Efforts worldwide have been done in order to design new technologies that are capable of combating or even...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.06.007
更新日期：2019-08-01 00:00:00
abstract：:Changes in the rate of DNA synthesis in spermatogenic cells after treatment of segments of rat seminiferous tubule at defined stages of epithelial cycle with benzo[a]pyrene (BP) or 7,12-methylbenz[a]anthracene (DMBA) were studied. The incorporation of labeled thymidine into DNA was used as a measure of the rate of DNA...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(89)90019-7
更新日期：1989-01-01 00:00:00
abstract：:The 2 pH dependent peaks formed in the Soret region by the treatment of reduced hepatic microsomes or purified cytochrome P-448 with ethyl isocyanide do not exhibit identical dependence on ethyl isocyanide concentration. This behavior and other facts regarding double Soret spectra can be explained by a simple expostul...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(78)90051-0
更新日期：1978-02-01 00:00:00
abstract：:The efficiency of multiplicity reactivation of T4 particles inactivated by platinum(II) complexes is very low. The same is true for marker rescue and functional survival of genes. This can be at least partly explained by the inability of most inactivated virus particles to introduce their DNA into the host cells as de...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(79)90166-2
更新日期：1979-12-01 00:00:00
abstract：:Vascular disease is a major cause of morbidity and mortality among transplanted recipients and cyclosporine (CsA) treatment has been consistently implicated in this event. In this study we assessed total blood homocysteine levels (tHcy), ecto-nucleotidase activities and adenine nucleotide/nucleoside levels searching f...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.06.011
更新日期：2010-10-06 00:00:00
abstract：:In cancer, a high flux of oxidants not only depletes the cellular thiols, but damages the whole cell as well. Epidemiological studies suggest green tea may mitigate cancers in human and animal models for which several mechanisms have been proposed. In the present investigation, the levels of cellular thiols such as re...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2004.06.006
更新日期：2004-10-15 00:00:00
abstract：:Many flavonoids have been shown to present good results for the treatment of gastric ulcers. Baicalein, a bioactive flavonoid derived from the Scutellaria baicalensis Georgi root, possesses several biological effects, such as anti-inflammatory and antioxidant. This study was conducted to assess the gastroprotective pr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.10.016
更新日期：2016-12-25 00:00:00
abstract：:p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs). Finding a correlation between AChE activity with the partition coefficient (log P) and the highest occupied molecular orbital (HOMO) energy of the compounds. ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.055
更新日期：2005-12-15 00:00:00
abstract：:We measured the response of HepG2 cells to the classic cytochrome (cyt.) P-450 inducers 3-methylcholanthrene (3-MC) and phenobarbital (PB), by evaluating oxidative and/or reductive metabolism of the nitroarenes, 1-NP and 1,6-dinitropyrene (1,6-DNP), in control and induced cells. In HepG2 cells, 3-MC induces ring-hydro...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(91)90057-e
更新日期：1991-01-01 00:00:00
