共查询到20条相似文献,搜索用时 15 毫秒
1.
N. J. Delraso D. R. Mattie C. S. Godin 《In vitro cellular & developmental biology. Plant》1989,25(11):1031-1038
Summary Primary rat hepatocyte suspension cultures (∼2×106 cells) exposed to solubilized 2,3,4-trimethylpentane at concentrations ranging from 7.9 to 31.5 mM under two different culture conditions resulted in a linear dose response, as determined by lactate dehydrogenase leakage
and viability data. A significant increase in the 2,3,4-trimethylpentane effective concentration 50 for primary hepatocytes
occurred when exposures were implemented in medium containing 0.05% albumin. The effective concentration 50 for hepatocytes
exposed to 2,3,4-trimethylpentane in medium lacking and containing albumin were 17.1 and 20.7 mM, respectively. Metabolite analysis by gas chromatography-mass spectrometry of supernatant (lacking or containing albumin)
and cell extracts from hepatocyte cultures exposed to 2,3,4-trimethylpentane for 4 h indicated the presence of three metabolites:
2,3,4-trimethyl-1-pentanol, 2,3,4-trimethyl-2-pentanol, and 2,3,4-trimethyl-1-pentanoic acid. Electron microscopic examination
of 2,3,4-trimethylpentane-exposed primary hepatocytes indicated ultrastructural changes which included abnormal condensed
chromatin association with the nuclear membrane, swollen mitochondria, increased amounts of cytoplasmic lipid, significant
los of microvilli from the cell surface, increased vacuolation, and increased numbers of peroxisomes. Although these changes
were observed under both culture conditions, they were more severe in cultures lacking albumin. This study indicates that
primary hepatocyte suspension cultures provide a useful system for rapidly identifying liver metabolites of selected test
compounds of interest.
Animals used in this study were handled in accordance with the principles stated in the Guide for the Care and Use of Laboratory
Animals, prepared by the Committee on Care and Usage of Laboratory Animals of the Institute of Laboratory Animals Resources,
National Research Council, DHHS, National Institute of Health publication 85–23, 1985, and the Animal Welfare Act of 1966,
as amended. This material has been funded wholly or in part by the United States Air Force under contract F33615-85-C-0532
to NSI Technology Services Corporation. It has been subject to review by the United States Air Force and it has been approved
for publication as a customer document. Mention of trade names or commercial products does not constitute endorsement or recommendation
for use. 相似文献
2.
J. Liu W. C. Kershaw C. D. Klaassen 《In vitro cellular & developmental biology. Plant》1990,26(1):75-79
Summary The effect of Zn-induced metallothionein (MT) on the toxicity, uptake, and subcellular distribution of cadmium (Cd) was examined in rat primary hepatocyte cultures and compared to results obtained earlier in this laboratory from intact animals. Hepatocytes were isolated and grown in monolayer culture for 22 h and subsequently treated with ZnCl2 (100 μM) for 24 h, which increased MT concentration about 15-fold. After Zn pretreatment, hepatocytes were exposed to Cd for 24 h. Cytotoxicity was assessed by enzyme leakage, intracellular potassium loss, and cellular glutathione content. The toxicity of Cd was much less in Zn-pretreated cells than in control cells, similar to that previously demonstrated in the intact animal. Zn pretreatment had no appreciable effect on the hepatocellular uptake of109Cd, but markedly altered its subcellular distribution, with more Cd accumulating in the cytosol and less in the nuclear, mitochondrial, and microsomal fractions. In the cytosol of Zn-pretreated cells, Cd was associated mainly with MT; in contrast, cytosolic Cd in control cells was mainly associated with non-MT macromolecules. Zn-induced changes in the subcellular distribution of Cd in vitro are identical to those observed in vivo in Zn-pretreated rats challenged with Cd. In summary, Zn pretreatment of rat primary hepatocyte cultures protects cells against Cd toxicity. Protection seems to be due to MT-promotes sequestration of Cd and reduction of the amount of Cd associated with critical organelles and proteins. These observations are similar to those noted in the whole animal. These results indicate that cultured hepatocytes are an ideal model for examining MT-induced tolerance to Cd hepatotoxicity. This work was supported by grant ES-01142, and WCK was supported by training grant ES-07079, both from the Public Health Service, Department of Health and Human Services. 相似文献
3.
4.
Cultured rat hepatocytes exposed to 2-acetylaminofl uorene (AAF), 2-aminofl uorene (AF) or N-hydroxy-2-acetylaminofluorene (N-OH-AFF) for 3 hrs resulted in an increase in DNA repair measured as unscheduled DNA synthesis, with N-OH-AAF > AAF > AF. Cytotoxic effects were only seen with N-OH-AAF above 10–6 M. -Naphthof avone increased the unscheduled DNA synthesis and cytotoxic effects of N-OH-AAF, whereas it decreased DNA repair and the covalent binding of AAF to cellular proteins. In contrast, very little effects of paraoxon were seen on the repair synthesis elicited by AAF, AF or N-OH-AAF. The addition of ascorbate reduced the covalent binding of AAF, the DNA repair synthesis caused by AAF and N-OH-AAF, and the cytotoxic effects of N-OH-AAF. The addition of pentachlorophenol or salicylamide all resulted in similar effects as ascorbate, through reduction of sulfation. Galactosamine, an inhibitor of glucuronidation, and the nucleophile GSH caused no or only minor effects of the activation of AAF, AF or N-OH-AAF as judged from the endpoints tested. These results are consistent with an arylnitrenium ion, a sulfate ester or a free radical as the arylamine metabolite causing cellular DNA damage, whereas the sulfate ester or a radical intermediate may be responsible for the cytotoxic effects of N-OH-AAF.Abbreviations AAF
2-acetylaminofluorene
- AF
2-aminofluorene
- N-OH-AAF
N-hydroxy-2-acetylaminofluorene
- cytochrome P-450
a collective term for all forms of the cytochrome P-450 polysubstrate monooxygenase
- DMSO
dimethyl sulfoxide
- HU
hydroxyurea
- S-9
9000 g supernatants
- LDH
lactate dehydrogenase
- UDS
unscheduled DNA synthesis
- ANF
-naphthoflavone
- GSH
glutathione
- PCP
pentachlorophenol
- MET
metyrapone
- PAR
paraoxon
- DEM
dimethylmaleate 相似文献
5.
This study describes the development of a simple, rapid and reproducible microassay for determining the intracellular LDH activity of rat hepatocytes present in a co-culture system with other cells. The procedure involves treatment of cellular homogenates with an anti-LDH antiserum that specifically inhibits the LDH activity of rat hepatocytes. The assay is performed in 96-well plates and LDH activity can be measured directly in the same wells using a colorimetric method. The difference in LDH activity values measured before and after antiserum incubation reflects the LDH content of the hepatocytes in the sample. The advantages of this method are the small number of cells required, a reduction in sample handling and the possibility of differentiating LDH activity in hepatic and non-hepatic cells. The possible applications of this technique as a parameter for biochemical data and as a test for cytotoxicity studies in co-cultures are also discussed. 相似文献
6.
Rim Timoumi Ines Amara Intidhar Ben Salem Salwa Abid‐Essefi 《Journal of biochemical and molecular toxicology》2020,34(8)
Insect growth regulator insecticides are a new class of pesticides, commonly used around the world to control insect damages. Among those compounds, we focused our interest on triflumuron (TFM), which is less toxic than other conventional insecticides. However, not much is known about its toxic effects on mammalian systems. Therefore, our study aimed toward evaluating the cytotoxic and genotoxic effects of TFM using two different cell lines, the human renal embryonic cells (HEK 293) and hepatocytes (Hep G2). We showed, according to the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, that TFM reduced significantly the cell viability and increased the reactive oxygen species generation, malondialdehyde levels, and mitochondrial membrane potential in both cell lines. The antioxidant system was disturbed as assessed by the increased activities in both catalase and superoxide dismutase. We demonstrated also, that TFM is an inductor of DNA damages quantified by the comet assay. Moreover, we showed an overexpression of proapoptotic Bax and a decrease in antiapoptotic Bcl‐2 expression. As a conclusion, we demonstrate that the liver presents the major target organ to TFM, in which the cytotoxicity and the genotoxic effects were significantly higher in hepatic cells than in renal cells and by consequence its uses must be controlled. 相似文献
7.
J M Bégué G Baffet J P Campion A Guillouzo 《Biology of the cell / under the auspices of the European Cell Biology Organization》1988,63(3):327-333
The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+)-cyanidanol-3 (Catergen) were evaluated in both human and rat hepatocytes in primary cultures. AFB1-induced acute toxicity was visualized by light microscope observation and quantified by measurement of lactic dehydrogenase activity in the medium. Human hepatocytes were susceptible to AFB1-induced cytotoxicity but no evident relationship between the concentration of mycotoxin and the extent of cellular damage was established. (+)-Cyanidanol-3 was not toxic at concentrations up to 2 x 10(-3)M, but no obvious protective effect from AFB1-induced injury was evidenced in human cells. By contrast, rat hepatocytes responded in a dose-related manner to AFB1. (+)-Cyanidanol was toxic at 10(-3)M, but even at this concentration exerted a strong protective effect against AFB1-induced cytotoxicity. Such species differences suggest the existence of metabolic differences in both AFB1 and (+)-cyanidanol-3 activating and deactivating mechanisms. 相似文献
8.
V Hadjimitova T Traykov R Bakalova V Petrova I Lambev H Ohba M Ishikawa Y Baba 《Luminescence》2004,19(6):319-321
The present study describes the application of several chemiluminescent (CL) methods for evaluation of antioxidant and immunomodulation effects of psychotropic drugs upon phagocytes: KO2-induced luminal-dependent CL for detection of superoxide anion radicals in a pure chemical system; PMA- and A23187-induced CL of peritoneal macrophages for detection of free radicals in cell suspension; and CL, produced by the luciferase-catalyzed luciferin + ATP reaction, for evaluation of cell viability before and after drug application. These methods provide also a way to investigate the location of drug action. It was found that the psychotropic drugs in fluence the 'oxidative burst' of macrophages through two mechanisms: by expression of drug antioxidant properties and/or by a direct immunomodulation effect. 相似文献
9.
The mechanisms of toxicity to isolated rat hepatocytes of Fe(II) and Fe(III) complexes of two structurally related naphthoquinones have been studied. All complexes were found to show a dose-dependent toxicity which precedes cell death. Within the naphthoquinone series the order of toxicity is Fe(II) > parent naphthoquinone > Fe(III). The iron complexes of 5-OH-1,4 naphthoquinone (5-OH-1,4 NQ; Juglone) are more toxic than the iron complexes of 2-OH-1,4 naphthoquinone (2-OH-1,4 NQ; Lawsone) indicating that the mechanisms of toxicity are different. Electrochemical studies on these complexes shows that 5-OH-1,4 NQ facilitates formation of stable semiquinone species while 2-OH-1,4 NQ does not. The low redox potential of 2-OH-1,4 NQ makes it a poor substrate for metabolism by reductases. 相似文献
10.
Balz V Hoheisel M 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2011,42(4):453-466
The present article illustrates the history of psychotropic drugs introduced in the German Democratic Republic (GDR) from 1945 onwards. We begin by examining the introduction of an anti-depressant and a tranquilizer at the university psychiatric clinic, Charité, in East Berlin. On the basis of patient files, we consider the monitoring routines, altered by the use of psychotropic drugs, and the difficulties that arose when these routines were translated into existing research programs. In the 1960s, attempts to evaluate the psychiatric practice were based on psychopathology whereas at the end of the 1960s there was a shift to “target symptoms”. 相似文献
11.
12.
A method for the primary culture of rat liver cells on collagen-coated dextran microcarriers is described. Ethoxycoumarin deethylase (EOD) activity 24 hr after inoculation was comparable for liver cells cultured on microcarriers and on collagen-coated dishes. Cells were cultured on microcarriers for up to 48 hr and retained 25% of the initial EOD-activity that was seen in freshly isolated liver cells. Microcarrier-attached hepatocytes were cocultured with BALB/c 3T3 cells to study the metabolism-mediated cytotoxicity of cyclophosphamide (CPA). In the absence of hepatocytes, growth of 3T3 cells was not affected by CPA at concentrations up to 3600 M. In coculture with hepatocytes, cytotoxicity of CPA was expressed in a time- and concentration-dependent manner. At high concentrations, CPA slightly depressed the EOD-activity of hepatocytes. Our results indicate that cocultivation of microcarrier-attached rat liver cells with target cells represents a valuable approach to the study of the metabolism-mediated toxicity of xenobiotics in vitro.Abbreviations CPA
cyclophosphamide
- EOD
Ethoxycoumarin deethylase
- FBS
fetal bovine serum
- HBSS
Hanks' balanced salt solution
- HEPES
N-2-Hydroxyethylpiperazine-N-2-ethanesulfonic acid
- PASA
Na-pyruvate, asparagine, serine, alanine
- 7-HC
7-hydroxycoumarin
This work was presented in part at the VIIIth Scandinavian Workshop on In Vitro Toxicology, Kongsvoll, Norway (1990). 相似文献
13.
An improved resazurin-based cytotoxicity assay for hepatic cells 总被引:2,自引:0,他引:2
McMillian MK Li L Parker JB Patel L Zhong Z Gunnett JW Powers WJ Johnson MD 《Cell biology and toxicology》2002,18(3):157-173
A simple resazurin-based cytotoxicity assay is presented for screening of cytotoxicity in hepatocytes and liver cell lines.
Human hepatoma (HepG2) cells in 96-well culture plates were exposed to known toxic (cisplatin, 5-fluorouracil, ethionine,
flufenamic acid, and diflunisal) and control (transplatin, 5-chlorouracil, methionine, and acetylsalicylic acid) compounds
for 1–3 days, and resazurin (5 μmol/L) was added. A conventional short-term (1 h) assay was first performed, where cytotoxicity
is indicated by decreased reduction of resazurin to its fluorescent product resorufin. Our improved assay consists of additionally
measuring fluorescence 2–4 days later, when cytotoxicity is indicated by a striking increase in the concentration of resorufin, resulting from two distinct processes. First, viable liver-derived cells slowly convert
resorufin to nonfluorescent metabolites. Fluorescence of control cell wells decreased to background during a 2- to 4-day exposure
to resazurin. This metabolism of resorufin was largely blocked by dicumarol and to lesser extents by disulfiram and SKF525a.
Second, dead or dying cells slowly convert resazurin to resorufin but do not further metabolize resorufin; thus this fluorescent
metabolite accumulates to high levels in wells with dead cells by 2 to 4 days. A similar increase in fluorescence associated
with cytotoxicity was observed in primary cultures of rat hepatocytes using the long-term resazurin-based assay. In addition
to an improved signal relative to the short-term assay, the inversion of the fluorescent signal from high = alive short-term
to high = dead long-term allows determination of two independent cytotoxicity endpoints after addition of one innocuous vital
dye.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
14.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):330-338
New hydrazone ligands (HL) derived from 5-substituted isatins and 1-(4-(2-methoxybenzyl)-6-arylpyridazin-3-yl)hydrazines and its complexes with Co(II) and Cu(II) were synthesized. The new hydrazones and their complexes were characterized by means of elemental, spectral analyses and magnetic studies. Primary cytotoxicity evaluation of HL 5a and the new complexes showed that these complexes could act as anticancer agents since they reduced the growth of samples of human tumour cell lines (HCT116(Colon), MCF7(Breast) and HELA(Cervix)) to ≤18.5 μg/mL for the new complexes. 相似文献
15.
Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide metabolites. These electrophilic species alkylate cell proteins and may be implicated in the pathogenesis of a number of toxic syndromes seen in patients receiving the parent aglycones. Whether acyl glucuronides also attack nuclear DNA is unknown, although the acyl glucuronide formed from clofibric acid was recently found to decrease the transfection efficiency of phage DNA and generate strand breaks in plasmid DNA in vitro. To determine if such a DNA damage occurs within a cellular environment, the comet assay (i.e. single-cell gel electrophoresis) was used to detect DNA lesions in the nuclear genome of isolated mouse hepatocytes cultured with clofibric acid. Overnight exposure to 50 microM and higher concentrations of clofibric acid produced concentration-dependent increases in the comet areas of hepatocyte nuclei, with 1 mM clofibrate producing a 3.6-fold elevation over controls. These effects closely coincided with culture medium concentrations of the glucuronide metabolite formed from clofibric acid, 1-O-beta-clofibryl glucuronide. Consistent with a role for glucuronidation in the DNA damage observed, the glucuronidation inhibitor borneol diminished glucuronide formation from 100 microM clofibrate by 98% and returned comet areas to baseline levels. Collectively, these results suggest that the acyl glucuronide formed from clofibric acid is capable of migrating from its site of formation within the endoplasmic reticulum to generate strand nicks in nuclear DNA. 相似文献
16.
We have previously synthesized various diazenecarboxamides (subsequently referred to as diazenes) that were cytotoxic to several
tumor cell lines. To increase their biological activity, the structure has been modified appropriately. In the present study
we examined the effects of N1-phenyl-N2-(2-pyridinylmethyl)diazenedicarboxamide (RL-337) obtained from the previously examined cytotoxic compound N1-phenyl-N2-(2-pyridinyl)diazenecarboxamide (JK-279), and compared them with those of diazene JK-279. Using a modified colorimetric MTT
assay, the cytotoxicity of RL-337 was determined on human cervical carcinoma HeLa cells, glioblastoma A1235 cells, and prostate
adenocarcinoma PC-3 cells. The possible synergistic effect of diazene RL-337 with cisplatin, doxorubicin, and vincristine,
and its influence on intracellular GSH content was examined on HeLa cells. Diazene RL-337 was cytotoxic against all three
human tumor cell lines, being more cytotoxic to HeLa cells than diazene JK-279. The higher efficacy of RL-337 than of JK-279
can be connected with higher basicity of the 2-picoline moiety present in the former diazene comparing with the pyridine fragment
that is a part of the latter. The diazene RL-337 acted synergistically with cisplatin, doxorubicin, and vincristine (diazene
JK-279 exhibited synergistic effect only with cisplatin). Glutathione (determined by Tietze's method) was not a target molecule
of diazene RL-337 (but was for JK-279, as shown earlier). After just 1 h treatment with diazene RL-337, the cells started
to lose membrane integrity. There was no cleavage of caspase-3 in RL-337-treated samples, and the majority of cells died 6
h after the treatment through necrosis (previously, apoptosis-like cell death was detected for diazene JK-279). Thus, although
diazenes JK-279 and RL-337 are very similar in their structure, they exhibit widely different biological activity. 相似文献
17.
Heggodu G. RohitKumar Kittur R. Asha Hulihalli N. KiranKumar Laxmi S. Inamdar 《Nucleosides, nucleotides & nucleic acids》2015,34(8):525-543
Circular dichroism, topological studies, molecular docking, absorbance, and fluorescence spectral titrations were employed to study the interaction of 4-morpholinopyrimido [4′,5′:4,5] selenolo (2,3-b) quinoline (MPSQ) with DNA. The association constants of MPSQ–DNA interactions were of the order of 104 M?1. Melting temperature, topological, and docking studies confirmed that the mode of interaction was by intercalation with preference to d(GpC)–d(CpG) site of DNA. Cytotoxicity studies showed the MPSQ-induced dose-dependent inhibitory effect on the proliferation of different cancer cells. Colon adenocarcinoma (COLO 205) cells are more sensitive among the cell lines tested, with an IC50 value of 15 μM. Flow cytometry revealed that MPSQ affects the cell cycle progression by arresting at G2M phase. Further, Annexin V staining, mitochondrial membrane potential assay, and caspase-3 activity assay confirmed that MPSQ leads to mitochondria-mediated apoptotic cell death in COLO 205 cells. 相似文献
18.
R. Bannach A. Valenzuela B.K. Cassels L. J. Núnez-Vergara H. Speisky 《Cell biology and toxicology》1996,12(2):89-100
Boldine, an aporphine alkaloid, was recently shown by us to exhibit potent antioxidant properties. We report here that boldine concentration-dependently inhibited the peroxidative (accumulation of thiobarbituric acid reactive substances) and lytic damage (trypan blue exclusion and lactate dehydrogenase leakage) to isolated rat hepatocytes induced by tert-butyl hydroperoxide (TBOOH). Boldine (200 mol/L) fully cytoprotected and completely prevented the peroxidation induced by TBOOH a concentrations equal to or lower than 0.87 mmol/L. However, at a peroxide concentration of 0.91 mmol/L, although boldine completely inhibited lipid peroxidation it largely failed to afford cytoprotection against TBOOH. TBOOH alone (0.83 mmol/L) caused an early (within 60 s) sudden decline of reduced glutathione (by 50%) and an equivalent increase in the levels of oxidized glutathione. Neither of these effects was prevented by the simultaneous addition of a cytoprotective and antioxidant concentration of boldine (200 mol/L). The delayed addition of boldine to the suspension (after 10 or 20 min), while effectively blocking any further increase in thiobarbituric acid reactive substances, totally failed to prevent the peroxide-induced loss in cell viability. Conversely, preincubation of the hepatocytes with boldine for 150 min (at which time no boldine could be detected in either intra- or extracellular spaces) prevented lipid peroxidation and was as effective in protecting the cells against the damage caused by the subsequent addition of TBOOH as the simultaneous addition of boldine and TBOOH to hepatocytes preincubated for 150 min under control conditions.Abbreviations DMSO
dimethyl sulfoxide
- GSH
reduced glutathione
- GSSG
oxidized glutathione
- LDH
lactic dehydrogenase
- TBARS
thiobarbituric acid reactive substances
- TBOOH
tert-butyl hydroperoxide 相似文献
19.
Hyperthermia (HT) in combination with anticancer drugs (ACDs) had proven to more efficacious in various cancers, although
efficacies vary according to chemotherapeutic compounds and cancer types. Presently there are few data that compares anticancer
efficacies among ACDs under hyperthermic conditions. Therefore, we selected three commonly used ACDs (quercetin, verapamil
and doxorubicin) and compared their antitumor effects when each was treated with 43°C HT exposure. Firstly, FM3A, a murine
breast cancer cell line, was treated with each ACD for 1 h followed by 43°C exposure for additional 1 h, and examined the
effects of: 1) each drug, 2) 43°C HT exposure, and 3) the combination of each drug and 43°C HT exposure for 1, 6 and 24 h.
The determined overall effects on FM3A cells were arrested cell proliferation, clonogenic efficiency and apoptosis. Pre-treatment
of FM3A cells to each ACD followed by 43°C HT exposure produced greater antitumor effects including suppressed cell proliferation,
reduced clonogenic efficiency and increased apoptotic cell death, compared to ACD treatment or HT exposure alone. Apoptotic
cell death occurred in a time-dependent manner. Among the ACDs, antitumor efficacies varied in the order of doxorubicin >
verapamil > quercetin. It was concluded that heat exposure during ACD treatment of caner cells may be an important factor
to get a better antitumor benefit, even though this benefit may differ from one drug to another. 相似文献
20.
The combination of co-cultivation of hepatocytes and epithelial cell lines with a newly developed perifusion system was used for in vitro studies on drug metabolism and cytotoxicity. This approach improved the viability and enhanced the induction of the biotransforming capacity of the hepatocytes. As demonstrated for the induction of 7-ethoxyresorufin O-deethylase activity by 3-methylcholanthrene or benzanthracene, co-cultured hepatocytes in the perifusion system responded more sensitively to these inducers than without perifusion, most likely owing to stable (steady-state) concentrations of the inducers under the former conditions and rapidly declining concentrations under the latter conditions. The perifusion approach rendered it possible to determine the kinetics of drug metabolism during single or sequential incubations. After induction with 3-methylcholanthrene and phenobarbital, phase I metabolism of lonazolac to the monohydroxylated product in perifused co-cultures closely (87%) approached the values reported for the in vivo production, whereas in stationary co-cultures only 52% could be reached. Likewise, cytotoxic effects could be detected more precisely in the perifused co-cultures. If cells were pretreated with 0.2 mmol/L galactosamine for 3 h, perifusion with increasing concentrations of menadione differentially killed epithelial RL-ET-14 cells and hepatocytes at low and high concentrations, respectively, while in stationary co-cultures no differential effect was observed and only the higher concentrations were cytotoxic for both cells. Prevention by incubation with S-adenosylmethionine of menadione cytotoxicity up to a menadione concentration of 250 mol/L was seen only in the perifused co-cultures, whereas in stationary cultures only a slight shift of the cytotoxic concentration exerting 50% cell damage to higher values was noted. These results demonstrate the versatile application of perifused co-cultures for studies on drug metabolism including induction of cytochrome P450-dependent enzymes and steady-state kinetics of biotransformation, as well as cytotoxic and protective effects of different drugs.Abbreviations BA
benzanthracene
- CC50 values
cytotoxic concentration exerting 50% cell damage
- EROD
7-ethoxyresorufin O-deethylase
- LDH
lactate dehydrogenase
- LON
lonazolac
- MC
3-methylcholanthrene
- PB
phenobarbital 相似文献