Abstract:
:NADPH-fortified human liver microsomes were examined with regard to ability to detoxicate several chemicals that do not require enzymatic oxidation to elicit a genotoxic response in a Salmonella typhimurium TA1535/pSK1002 system where umu response is used as an indicator of DNA damage. Microsomes did not affect the response seen with daunomycin, mitomycin C, 2,4,7-trinitro-9-fluorene, 1-nitropyrene, doxorubicin, 1-methyl-3-nitro-1-nitrosoguanidine, 2-nitrofluorene, or 1-ethyl-3-nitro-1-nitrosoguanidine (cited in order of decreasing umu response per mol). Human and rat liver microsomes did inactivate 1,3-, 1,6-, and 1,8-dinitropyrene; with human liver microsomes the activity of 1,3-dinitropyrene was most strongly inhibited, while with rat liver microsomes the genotoxicities of all three dinitropyrenes were inhibited to a similar extent. NADPH-cytochrome P-450 reductase was demonstrated to inactivate 1,6- and 1,8-dinitropyrene but not 1,3-dinitropyrene. Both rat cytochrome P-450 beta NF-B (P-450 IA1) and P-450ISF-G (P-450 IA2) inactivated 1,3-dinitropyrene, with the former being more effective. Correlation studies done with liver microsomes prepared from variously treated rats and immunoinhibition studies suggest that cytochrome P-450 beta NF-B and P-450ISF-G are both involved in the detoxication of all three of the dinitropyrenes in rat liver microsomes. In a series of assays done with various human liver microsomal preparations, the inactivation of the three dinitropyrenes was not correlated to each other at all. Correlation analysis and inhibition studies with 7,8-benzoflavone and antibodies indicate that human cytochrome P-450 enzymes in the IA family are most effective in detoxicating this compound; the contribution of cytochrome P-450PA (P-450 IA2, the phenacetin O-deethylase) is deemed more important, but a role for the small amount of cytochrome P1-450 (P-450 IA1) in the liver cannot be ruled out. In contrast to the case of 1,3-dinitropyrene, the inactivation of 1,6-dinitropyrene is well correlated with levels of cytochrome P-450NF (P-450 IIIA4, nifedipine oxidase) and its catalytic activities. The inactivation of 1,8-dinitropyrene was not correlated with any of the above parameters and only correlated with the conversion of benzo(a)pyrene to its 3-hydroxy and 4,5-dihydrodiol products, for which the principal enzymes involved in human liver are unknown. Thus, distinct human cytochrome P-450 enzymes are involved in the detoxication of different dinitropyrene congeners, and the situation appears to contrast with that in rat liver.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Shimada T,Guengerich FPsubject
Has Abstractpub_date
1990-04-01 00:00:00pages
2036-43issue
7eissn
0008-5472issn
1538-7445journal_volume
50pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-2069
更新日期:2020-04-01 00:00:00
abstract::Copper plays an essential role in promoting angiogenesis. Tumors that become angiogenic acquire the ability to enter a phase of rapid growth and exhibit increased metastatic potential, the major cause of morbidity in cancer patients. We report that copper deficiency induced by tetrathiomolybdate (TM) significantly imp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of establ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1621
更新日期:2017-04-01 00:00:00
abstract::Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0324
更新日期:2018-07-15 00:00:00
abstract::Sulfated macromolecules synthesized in tumor and mucosa tissues derived from colorectal cancer patients were labeled with [35S]sulfate and separated into two fractions on DEAE-Sephacel: the slightly acidic peak (peak I) was eluted with 0.2 M NaCl and the highly acidic peak (peak II) was eluted with 0.5 M NaCl. A total...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-05-15 00:00:00
abstract::A correlation exists between the ability of tumor cells to aggregate platelets and their tendency to metastasize. Tumor cell-induced platelet aggregation (TCIPA) facilitates the embolization of the vasculature with tumor cells and the formation of metastatic foci. It is well documented that matrix metalloproteinases (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::An accurate method of classification of the surface membrane characteristics of blast cells from patients with acute lymphoblastic leukemia would allow a more definitive study of the nature of this disease. Monoclonal antibodies have been produced to the surface antigens of leukemic blasts form a patient with high-ris...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::An in vivo-in vitro approach to studying neoplastic development in carcinogen-exposed rat fibroblasts was evaluated. In the model described, oncomodulin (Mr 12,000; pI 3.9), a tumor-associated and Ca2+-binding protein, was used as a specific marker of malignant transformation. A rapidly proliferating granulation tissu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-15 00:00:00
abstract::Loss of chromosome 19p is one of the most frequent allelic imbalances in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes within this region. In this study, we investigated a role in ESCCs for a candidate tumor suppressor gene located at 19p13.3, the Ras-like sm...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-2663
更新日期:2013-04-01 00:00:00
abstract::Oligodendrogliomas are a specific subtype of brain tumor of which the majority responds favorably to chemotherapy. In this study, we made use of expression profiling to identify chemosensitive oligodendroglial tumors. Correlation of expression profiles to loss of heterozygosity on 1p and 19q, common chromosomal aberra...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1886
更新日期:2005-12-15 00:00:00
abstract::An androgen-dependent tumor (SCC8 tumor) was obtained by inoculating an androgen-responsive cell line derived from the androgen-responsive Shionogi carcinoma 115 (SC115) into mice and then treating the mice with testosterone propionate (TP) at a pharmacological dose (400 micrograms/day). The SCC8 tumor differed in his...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::We evaluated the usefulness of L-dopa decarboxylase (DDC) as a tumor marker of neuroendocrine (NE) cell differentiation by measuring its expression in 432 human tumors of diverse types and origins. A subset of these tumors and cell lines derived from them also were studied for expression of two other general NE cell m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-15 00:00:00
abstract::Groups of 15 mice of three different laboratory strains (BALB/c, C3H/He, DBA/2) were fed on a low iron diet (5 mg iron/kg diet), and three similar groups of 15 mice were maintained on a normal iron diet (312 mg iron/kg diet). When the low iron diet group became iron deficient, tumor cells (5 x 10(5) cells/mouse) of CA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-04-15 00:00:00
abstract::Human breast cancer (HBC) cell growth suppression by okadaic acid (OA) was previously found to involve elevated expression of oncogenes c-myc and c-fos and apoptosis. Since, c-Myc influences diverse pathways of cell growth, we hypothesized that elevated levels of c-Myc are involved in HBC growth suppression. Here, we ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2505
更新日期:2007-11-01 00:00:00
abstract::Cultured human T-cell leukemia lymphocytes have enhanced sensitivity to growth inhibition by deoxyadenosine. We have used flow cytometry to investigate the mechanism of deoxyadenosine toxicity in cultured T-leukemic cells. Comparative studies on deoxyadenosine-resistant Epstein-Barr virus-transformed B-lymphocyte cell...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-12-01 00:00:00
abstract::The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the growth of epithelial cells from rat, hamster, and human respiratory tract has been measured by monitoring colony formation and cross-linked envelope formation in culture. TPA and its active derivatives stimulated colony formation of rat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-01-15 00:00:00
abstract::Tumor necrosis factor (TNF) acts via a cell surface receptor to induce a variety of cellular events including cytolysis, differentiation, and mitogenesis. The mechanisms underlying the cell specific actions of TNF are not known. In the present study, postreceptor events associated with the autoinduction of TNF express...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-11-15 00:00:00
abstract::To assess the in vivo behavior of cytotoxic agents linked to antibodies, deferoxamine, known to form stable chelates with 67Ga, was conjugated with monoclonal antibodies using three different methods. One method used a homocoupling reagent, glutaraldehyde, whereas two other methods used heterocoupling reagents, N-succ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Angiogenesis is characteristic of solid tumor growth and a surrogate marker for metastasis in many human cancers. Inhibition of tumor angiogenesis using antiangiogenic drugs and gene transfer approaches has suggested the potential of this form of therapy in controlling tumor growth. However, for long-term tumor-free s...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1786
更新日期:2004-03-01 00:00:00
abstract::Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1005
更新日期:2004-10-01 00:00:00
abstract::1-beta-D-Arabinofuranosylcytosine (araC) is an effective drug in the i.p. therapy of ovarian carcinoma but little is known of its transport and metabolism in this tumor. Influx of araC at 1 microM into cultured human ovarian carcinoma cells (CI 80-13S) was largely inhibited by nanomolar concentrations of the nucleosid...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-01-15 00:00:00
abstract::Three Burkitt's lymphoma cell lines were studied for their response to cis-diamminedichloroplatinum(II) (cis-DDP) and L-phenylalanine mustard (L-PAM) with the objective of relating cytotoxicity to DNA cross-linking in human cells. Cytotoxicity was measured by cell proliferation and colony formation assays. DNA interst...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::The influence of microtubule-associated proteins on the interaction of vincristine with microtubules and tubulin was examined. Microtubules containing associated proteins were prepared in vitro from tubulin preparations which contained the proteins or from pure 6S tubulin and isolated microtubule-associated proteins. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-05-01 00:00:00
abstract::Infection with Helicobacter pylori is a major cause of gastric cancer (GC). The association likely has been underestimated in the past due to disease-related clearance of the infection. On the other hand, only a minority of the infected individuals develop GC, and better risk stratification is therefore highly desirab...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0596
更新日期:2009-08-01 00:00:00
abstract::Chronic exposures to cadmium compounds are carcinogenic. It was hypothesized that the development of resistance to cadmium may drive carcinogenesis. This is achieved by selection of resistant cells in which the apoptotic response is significantly attenuated. The induction of cadmium resistance in rat lung epithelial c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3771
更新日期:2007-03-01 00:00:00
abstract::Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell and its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility and deformability, lending them the flexibility to disseminate and navigate through dif...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3131
更新日期:2019-09-15 00:00:00
abstract::The adoptive transfer of recombinant-methionyl human interleukin 2 (rIL-2)-activated autologous peripheral blood mononuclear lymphokine-activated killer (LAK) cells to cancer patients is being evaluated as an alternative to conventional cancer therapy. We have independently developed an alternative regimen to previous...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This stu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::Biochemical quantitation of estrogen receptors has been used to predict prognosis in breast cancer. Immunocytochemical analysis of estrogen receptors correlates with biochemical analysis but has very few follow-up studies in the literature to validate it as a prognostic indicator. 257 patients were followed for up to ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-15 00:00:00