Abstract:
:The pharmacokinetics of N-nitrosodimethylamine was studied in patas monkeys following i.v. doses of 0.5, 1.0, and 5.0 mg/kg and a p.o. dose of 1.0 mg/kg, and in Swiss mice at i.v. doses of 1.0 and 2.0 mg/kg. In the patas monkey the pharmacokinetics was linear over the i.v. dose range studied. The mean clearance (Cl), steady-state volume of distribution (Vss), mean residence time, and elimination half-life (t 1/2) were 103.3 +/- 26.7 (SD) ml/min, 3061 +/- 821 ml, 30.8 +/- 10.8 min, and 21.1 +/- 8.5 min, respectively. Assuming that the pharmacokinetics was linear at the p.o. dose used, the p.o. bioavailability of N-nitrosodimethylamine in the monkey was 49%. The pharmacokinetics was also linear in mice, and the average Cl, Vss, mean residence time, and t 1/2 were 3.81 ml/min, 21.0 ml, 5.5 min, and 11.9 min, respectively. These data and data for rats, hamsters, rabbits, dogs, and pigs taken from the literature were used to scale Cl and Vss to body weight using the allometric equation. The resulting equation for Cl was Cl = 49.7B0.998 and the equation for Vss was Vss = 748B1.05 where B is body weight in kg. The fit of the data to the equation was excellent in both cases. Using these equations and assuming a body weight of 70 kg for humans, the Cl and Vss for N-nitrosodimethylamine in humans are estimated to be 3450 ml/min and 64,800 ml, respectively.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gombar CT,Harrington GW,Pylypiw HM Jr,Anderson LM,Palmer AE,Rice JM,Magee PN,Burak ESsubject
Has Abstractpub_date
1990-07-15 00:00:00pages
4366-70issue
14eissn
0008-5472issn
1538-7445journal_volume
50pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensiti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0036
更新日期:2005-09-01 00:00:00
abstract::Neuroblastoma is a neural crest-derived embryonal malignancy, which accounts for 13% of all pediatric cancer mortality, primarily due to tumor recurrence. Therapy-resistant cancer stem cells are implicated in tumor relapse, but definitive phenotypic evidence of the existence of these cells has been lacking. In this st...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-4056
更新日期:2013-07-01 00:00:00
abstract::PE-35 mouse monoclonal antibody (MoAb) (IgG1) detecting an epithelial antigen with a molecular weight of 35,000 was characterized serologically. Immunoperoxidase staining and double immunoenzymatic staining showed that PE-35 antigen is predominantly on nonlymphoid cells in the medulla of thymus. By immunoelectron micr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to DNA alkylating species via two different alpha-hydroxylation pathways. Methylene hydroxylation leads to DNA methylation, whereas methyl hydroxylation yields DNA pyridyloxobutylation. We have developed a high-pressure liquid chromatography assay utili...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::Two human erythroleukemia cell lines, HEL and K562, express transglutaminase activity. The enzyme was identified as a tissue transglutaminase following chromatographic purification. All-trans-retinoic acid (10 microM) stimulated differentiation in HEL cells as judged by a 4-fold increase in hemoglobin content and a re...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-12-15 00:00:00
abstract::MYC exerts both positive and negative functions in cancer cells, such that its procancerous effects are unmasked only after its anticancer effects are blocked. Here we used multiple mouse models of lung adenocarcinoma to identify genetic events that can cooperate with MYC activation to promote the genesis of non-small...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-3590
更新日期:2011-03-15 00:00:00
abstract::The invasive transformation of A-459 lung epithelial carcinoma cells has been linked to the autocrine regulation of malignant phenotypic changes by transforming growth factor beta (TGF-beta). Here we demonstrate, using stable 13C glucose isotopes, that the transformed phenotype is characterized by decreased CO2 produc...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Placenta growth factor (PlGF) is a mitogen for endothelial cells that can potentiate the growth and permeabilizing effects on endothelium of vascular endothelial growth factor. Here we report that hypoxia induces the expression of both PlGF mRNA and protein in immortalized/transformed mouse embryonic fibroblasts (mEFs...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-15 00:00:00
abstract::Plasma membrane preparations from Chinese hamster lung cells, which are resistant to the antitumor agent Adriamycin, were analyzed using fluorescence polarization of the membrane lipid probe trans-parinaric acid. The results of these studies reveal that membranes from several drug-resistant isolates have a substantial...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::The human colon cancer cell line HCT does not express any detectable HLA class I antigens on the cell surface. RNA blot analyses showed that HCT cells synthesize easily detectable levels of heavy chains as well as beta 2-microglobulin (beta 2m) transcripts. Experiments of immunoprecipitation revealed the presence of i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint path...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3927
更新日期:2007-02-01 00:00:00
abstract::Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per mol...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-08-15 00:00:00
abstract::We previously reported that the thermosensitivity of tumor cells can be increased when the intracellular pH is lowered by inhibiting Na+/H+ exchange through the plasma membrane with amiloride (3,5-diamino-6-chloro-N-(diamino methylene)pyrazinecarboxamide) or its analogues and HCO3-/Cl-exchange with 4,4-diiothiocyanato...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Dysregulation in patterns of alternative RNA splicing in cancer cells is emerging as a significant factor in cancer pathophysiology. In this study, we investigated the little known alternative splice isoform survivin-3B (S-3B) that is overexpressed in a tumor-specific manner. Ectopic overexpression of S-3B drove tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0036
更新日期:2013-09-01 00:00:00
abstract::The notion that nuclear factor-kappaB (NF-kappaB) is a tumor-promoting transcription factor has become a widely accepted dogma in biology. However, recent findings suggest an inhibitory role for NF-kappaB in carcinogenesis and tumorigenesis. Although the tumor suppressor-like effect of NF-kappaB remains to be rigorous...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-07-1576
更新日期:2007-12-01 00:00:00
abstract::Aflatoxicol, R0, was isolated from Mt. Shasta strain rainbow trout (Salmo gairdneri), and liver homogenates were incubated with aflatoxin B1. Its identity was confirmed by mass, infrared, and ultraviolet spectrometry. The structure was identical to one of the diastereomers prepared by chemical reduction of aflatoxin B...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-06-01 00:00:00
abstract::The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor trans...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::We have previously presented evidence that a transient block to DNA replication induces an aberrant form of DNA synthesis. The most feasible explanation for this data is that the block to DNA replication results in some segments of the chromosomal DNA being replicated more than once in a single cell cycle. This form o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::Mutations of the tumor suppressor E-cadherin and overexpression of the receptor tyrosine kinase epidermal growth factor receptor (EGFR) are among the most frequent genetic alterations associated with diffuse-type gastric carcinoma. Accumulating evidence suggests a functional relationship between E-cadherin and EGFR th...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1588
更新日期:2008-02-01 00:00:00
abstract::Previous laboratory investigations, case reports, and a hospital-based case-control study have suggested that marijuana use may be a risk factor for squamous cell head and neck cancer. We conducted a population-based case-control study to determine whether marijuana use is associated with the development of oral squam...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-03-3425
更新日期:2004-06-01 00:00:00
abstract::Tumor cell-derived selectin ligands mediate contact to the endothelium, platelets, and leukocytes through binding to selectins that facilitates metastasis. Here, we describe the mechanism of how endogenous (non-tumor derived) selectin ligands contribute to metastasis using α(1,3)fucosyltransferase 7 (Fuc-TVII(-/-))-de...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0946
更新日期:2014-02-01 00:00:00
abstract::Membranes from a B16 murine melanoma clone of high experimental metastatic capacity show increased amounts of pertussis toxin (PT) substrate when compared to a low metastatic counterpart. Using specific antibodies, we identified Gi2 as the PT-sensitive G-protein uniquely abundant in highly metastatic cells. ADP ribosy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (Cl-F-ara-A) is a new deoxyadenosine analogue that is resistant to phosphorolytic cleavage and deamination. Studies with a variety of cell lines demonstrated that Cl-F-ara-A is a potent cytotoxic agent; in cell-free systems, its triphosphate (Cl-F-ara-ATP) i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-07-15 00:00:00
abstract::Molecular insights into how chronic stress affects lung tumorigenesis may offer new routes to chemoprevention. In this study, we show that chronic stress in mice chemically or genetically initiated for lung cancer leads to the release of norepinephrine and other catecholamines, thereby promoting lung tumorigenesis. Me...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0990
更新日期:2016-11-15 00:00:00
abstract::Dioxin and pesticides with xenoestrogenic activity are environmental contaminants that are suspected of promoting human diseases such as cancers. However, few studies have addressed the molecular consequences of a combination of these contaminants, a situation that is likely to occur in the environment. We investigate...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-05-15 00:00:00
abstract::Various chemical compounds have been described to induce photosensitization of tumor cells resulting in cell death. We studied the effect of merocyanine-540 (MC-540) on both leukemic and normal bone marrow (BM) cells. Acute promyelocytic leukemia (HL-60) and common acute lymphoblastic leukemia antigen-positive non-T, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::In order to investigate the early cellular changes in liver associated with furan cholangiocarcinogenesis, young adult male Fischer 344 rats were administered furan by gavage once a day, 5 days a wk for 2 to 3 wk at doses ranging from 15 to 60 mg/kg of body weight per day. The most conspicuous feature observed in the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::Retroviral-mediated delivery of the P140K mutant O(6)-methylguanine-DNA methyltransferase (MGMT(P140K)) into hematopoietic stem cells (HSC) has been proposed as a means to protect against dose-limiting myelosuppressive toxicity ensuing from chemotherapy combining O(6)-alkylating agents (e.g., temozolomide) with pseudo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0320
更新日期:2008-08-01 00:00:00
abstract::Tumorigenesis can arise from inappropriate activation of developmental genes in mature tissues. Here, we show that the developmental regulator Six1 is overexpressed in ovarian carcinoma cell lines (OCC) compared with normal ovarian surface epithelium. As observed in other cancers, Six1 overexpression in OCC leads to i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3755
更新日期:2007-04-01 00:00:00