Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 343 records · Page 19Linked to original sources

PubMed1999

[General anesthesia for a patient with primary aldosteronism complicated with hypertrophic nonobstructive cardiomyopathy].

We report a patient with primary aldosteronism (PA) complicated with hypertrophic nonobstructive cardiomyopathy (HNCM) who underwent resection of a left adrenal tumor. Amrinone was administered to improve the features of congestive heart failure induced by retention of body fluid. Maintaining adequate preload and afterload and preventing excessive increases in contractility are important in the anesthetic management of patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the preoperative diagnosis may be HNCM, stenosis of the left ventricular outflow tract may occur due to hemodynamic changes during surgery. Therefore amrinone is not often used for patients with HNCM. We inserted a pulmonary arterial catheter (Swan-Ganz CCO Thermodilution Catheter) and measured the cardiac output continuously to monitor hemodynamic changes. The symptoms of pulmonary edema were diminished one month after the surgery. These findings suggest that the increased blood volume induced by PA is a main factor aggravating preoperative congestive heart failure with HNCM.

Adrenal Glands↗

PubMed1999

[Treatment of advanced testicular cancer and toxicity of chemotherapy].

To assess the efficacy and toxicity of chemotherapy for advanced germ cell tumors, 115 patients with testicular and extragonadal germ cell tumors were reviewed. Five-year survival rates of 19 seminoma patients and 96 non-seminoma patients were 84% and 68%, respectively. According to the analysis using three sets of prognostic criteria, Indiana University Classification, International Germ Cell Consensus Classification and K Classification, the 5-year survival rate of poor-prognosis patients was 42-45%. BEP regimen (bleomycin, etoposide and cisplatin) salvaged with VIP (etoposide, ifosfamide and cisplatin) would be the standard therapy for advanced germ cell tumors since high-dose chemotherapy had no advantage on survival over the standard-dose regimen. Early serious toxicities were observed in 18 patients (15.7%), including pulmonary fibrosis, respiratory distress, and sepsis. Poor performance status and prior radiotherapy were risk factors for fatal adverse effects. In terms of late toxicites, out of 76 patients in complete remission for at least one year after cessation of chemotherapy, 31 had numbness of extremities and 29 had tinnitus. Serial semen analyses of 38 patients showed continuous azoospermia or severe oligozoospermia in 22. These data indicated that less toxic therapy was required for good-risk patients to improve the quality of life, while more intensive therapy for poor-risk patients to be cured. Several prognostic criteria should be utilized to properly distinguish good- from poor-risk patients, and decide how to treat each patient.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Successful therapy of myelodysplastic syndrome with menatetrenone, a vitamin K2 analog.

Although vitamin K2 is an inducer of the in vitro differentiation of myeloid leukemic cell lines, its clinical efficacy in the treatment of myelodysplastic syndrome (MDS) is unclear. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to an 80-year-old woman with MDS (refractory anemia) heavily dependent on red-cell transfusions. The patient's pancytopenia gradually improved, and she became transfusion-independent after 14 months. Pancytopenia recurred when menatetrenone was discontinued but recovered again with readministration. Administration of menatetrenone at a dose effective in improving osteoporosis may also be useful in restoring hematopoiesis in MDS patients, possibly by way of inducing differentiation.

Aged↗

PubMed1998

Outcomes of stent-graft treatment of false lumen in aortic dissection.

BACKGROUND: Stent-graft treatment for aortic disease promises to lead to a less invasive therapy than conventional surgical therapy. However, this treatment has not been established as a therapy for aortic dissection. The aim of this study was to examine the effect of stent-graft treatment of aortic dissection, as measured by follow-up data on entry site closure, clotting in the false lumen, and the outcome of the false lumen from the acute to chronic phase after operation. METHODS AND RESULTS: We used a stent-graft of our own design to close the entry site of aortic dissection in 21 cases: 9 were acute (< 14 days), 8 subacute (< 6 months), and 4 chronic (> 6 months). Nine were type A and 12 were type B. In 15 cases, the stent-graft was inserted through the transverse arch, which had been surgically opened under median sternotomy. In the other 6 cases, the stent-graft was inserted by means of a transcatheter through a femoral artery. Using computed tomographic scans, we followed and examined clot formation in the false lumen and reduction in size of the false lumen at 3 levels: at the level of maximum aortic diameter, at the distal end of the stent-graft, and 50 mm distal to the stent-graft. The entry sites were successfully closed in 19 cases (90.4%); in the remaining 2 (both treated with a transcatheter) there was perigraft leakage into the false lumen. The hospital mortality rate of these stent-graft treatments was 14.3% (3 of 21). At 2 weeks after operation, the false lumen had completely clotted, respectively, in 100%, 77%, and 38% of cases at the 3 measurement levels. Substantial shrinkage (> 50% in diameter) of the false lumen at 6 months after the operation was observed in 72%, 60%, and 38% of cases at the respective levels. Shrinkage of the false lumen was particularly enhanced in patients treated within 6 months from the onset of dissection: The false lumen shrank by > 50% in 93%, 75%, and 50% of patients. CONCLUSIONS: In cases of aortic dissection, the stent-graft is an effective tool for closing the entry site and promoting clot formation in the false lumen and for reducing the size of the false lumen within 6 months of the onset of dissection if the entry site has been closed.

Adult↗

PubMed1998

Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high affinity very late antigen-4.

It has been shown that cells with high affinity very late Ag (VLA)-integrins have up-regulated expression of a beta1-subunit epitope, which is detected by 15/7 mAb. In this study, we demonstrate that soluble VCAM-1 (sVCAM-1) exhibits chemotactic activity of T cells with high affinity VLA-4 against VCAM-1, such as Jurkat T cells and IL-2-dependent T cells. Moreover, we found that T cells in the synovial fluid show high basal migration in the absence of sVCAM-1, compared with peripheral blood T cells in patients with rheumatoid arthritis. Among T cells in the synovial fluid, CD45RO+ memory T cells, in response to sVCAM-1, showed a much higher than basal migratory response when compared with CD45RA+ naive cells, while no significant difference was observed between CD4+ and CD8+ T cells. The chemotactic activity of sVCAM-1 is inhibited in the presence of anti-VCAM-1 and anti-VLA-4, which interfered with the binding between VCAM-1 and VLA-4. Inhibition studies using various kinase inhibitors (C3 exoenzyme, KN62, and H7) show that Rho, Ca2+/calmodulin-dependent kinase II, and protein kinase C are involved in signal transduction in sVCAM-1-induced chemotaxis, respectively, whereas tyrosine kinase seems to play a lesser role, since genistein showed only partial inhibition of T cell chemotaxis. Western blot analysis using an anti-phospho-serine mAb (MO82) reveals that Ser82 in the vimentin is phosphorylated specifically by Ca2+/calmodulin-dependent kinase II through sVCAM-1 activation in the IL-2 dependent T cells. Collectively, by inducing migration and recruitment of T cells through several kinase activations, sVCAM-1 contributes to the development of the inflammation of synovial lesion.

Adult↗

PubMed1998

Tumor necrosis factor-beta is associated with thymic apoptosis during acute rejection.

BACKGROUND: Intrathymic events undergoing allograft rejection remain undefined. The present study investigated the role of tumor necrosis factor-beta on acute thymic involution in rat hepatic allograft recipients during rejection. METHODS: Apoptosis and cellular phenotypic changes in the thymus were studied after hepatic transplantation. RESULTS: Thymocytes in both the medulla and cortex were sparse during acute rejection. Phenotypically, CD4+CD8+ T cells decreased significantly, whereas there were relative increases in CD4-CD8-, CD4+CD8-, and CD4-CD8+ T cells in untreated allograft recipients. Additionally, thymic apoptosis was found by in situ DNA end labeling and electron microscopy. Apoptotic cells were predominantly distributed in the cortex. Biologic lymphotoxin (tumor necrosis factor-beta)/tumor necrosis factor-alpha cytotoxic activity in the serum was significantly increased in untreated hepatic allograft recipients. Tumor necrosis factor-beta mRNA was detected in untreated allograft livers, and intraperitoneal administration of recombinant human tumor necrosis factor-beta induced extensive apoptosis of thymocytes in vivo. In contrast, no significant thymic involution was observed in donor-specific blood transfusion-treated allograft and isograft recipients. Intraperitoneal administration of rabbit anti-human tumor necrosis factor-beta polyclonal antibody or recombinant human interleukin-10 inhibited thymic apoptosis in untreated hepatic allograft recipients. CONCLUSIONS: Allograft rejection, but not donor-specific transfusion-induced immunologic unresponsiveness, is associated with thymic involution, a process that may be mediated by tumor necrosis factor-beta.

Acute Disease↗

PubMed1998

Molecular analysis of mutations induced by acrolein in human fibroblast cells using supF shuttle vector plasmids.

Types of mutations induced by acrolein in the supF gene on the shuttle vector plasmid pMY189 replicated in normal human fibroblast cells were examined. Base sequence analysis of 92 plasmids with mutations in the supF gene revealed that the majority of the mutations were base substitutions (76%) and the others were deletions and insertions (24%). Single base substitutions were most frequently found (46%), while multiple base substitutions were 18% and tandem (two adjacent) base substitutions were 12% of the mutations. Of the base substitution mutations, G:C to T:A transversions were 44% and G:C to A:T transitions were 24%. The mutations were distributed not randomly but located at several hotspots. Acrolein produced DNA intra-strand cross-links between guanine residues, which might be responsible for rather high induction of the tandem base substitution mutations.

Acrolein↗

PubMed1998

Development of a highly sensitive chemical method for detecting alpha2-->8-linked oligo/polysialic acid residues in glycoproteins blotted on the membrane.

A highly sensitive chemical method for detecting alpha2-->8-linked oligo/polysialic acid (oligo/polySia) chains was developed, including (i) periodate oxidation, reduction with sodium borohydride, and subsequent acid hydrolysis, giving rise to C7 analogues and intact C9 compounds from nonreducing terminal and internal sialic acid residues, respectively; (ii) fluorescent labeling of these C7 and C9 compounds with 1,2-diamino-4,5-methylenedioxybenzene (DMB); and (iii) quantitation of theseDMB derivatives on fluorometric high-performance liquid chromatography. As little as 1 ng of internal sialic acid residues of oligo/polySia chains, the existence of which indicates the presence of oligo/polySia structure, was detectable by this method. This fluorometric C7/C9 analysis was successfully applied to glycoproteins blotted onto a slit of polyvinylidene fluoride membranes and suggested the presence of some novel oligoSia-containing glycoproteins in pig embryonic brains.

Animals↗

PubMed1998

Prothrombin fragment 1 + 2 measures treatment effect in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis. The anticoagulant management of APS thrombosis remains controversial. Few reports on markers of in vivo activation of coagulation have been reported. To determine whether plasma levels of prothrombin fragment 1 + 2 (F1 +2) correlate with thrombotic risk and treatment effect in patients with APS, plasma F1 + 2 levels were followed in 57 patients with this syndrome for more than 2 years. Clinical findings were also observed in these patients. Plasma levels of F1 + 2 in patients with APS were significantly higher when compared with control subjects (p<.05). These results suggest patients with APS are in a hypercoagulable state. Plasma levels of F1 + 2 significantly decreased following treatment with either aspirin, or aspirin plus warfarin (p<.05 and p<.01, respectively). Recurrent thromboses or spontaneous abortions occurred in all eight patients whose plasma levels of F1 + 2 remained higher than 1 nmol/l after treatment with either aspirin alone or no anticoagulants. These patients were subsequently treated with warfarin as well as aspirin, and plasma levels of F1 + 2 decreased to less than 1 nmol/l, with no additional thrombotic events over the remainder of the 2-year follow-up. No fatal bleeding was observed in treated patients. Our results suggest plasma levels of F1 + 2 are useful indicators of successful treatment. It is also suggested that warfarin plus mini-dose aspirin therapy is effective for patients with APS to protect from recurrent thromboses without harmful side effects. Further, prospective cohort studies are needed to substantiate these associations.

Antiphospholipid Syndrome↗

PubMed1998

Induction of KDNase Sm, a deaminoneuraminic acid (KDN) residue-specific sialidase from Sphingobacterium multivorum, using synthetic KDN-glycosides.

Various aryl and alkyl alpha-glycosides of KDN were synthesized and tested as substrates for their susceptibility to a deaminoneuraminic acid (KDN)-specific sialidase from Sphingobacterium multivorum, designated KDNase Sm. The synthetic KDN-glycosides were all hydrolyzed by the action of KDNase Sm. A hydroxyl group at C-5 position of KDN was required for the recognition by the enzyme, and was shown not to be replaced by an amino- or an acylamino group for the enzymatic recognition. These synthetic KDN-glycosides were also examined for their inducing activity of KDNase in S. multivorum and were shown to induce the KDNase activity effectively when the bacterium was cultured minimum salt medium containing both 0.1% glucose and 0.1% various KDN-glycosides. No KDNase activity was induced by the KDN-glycosides without 0.1% glucose. This is the first case of using synthetic KDN-glycosides as inducers of KDNase Sm.

Carbohydrate Conformation↗

PubMed1998

A selective switch-on system for self-renewal of embryonic stem cells using chimeric cytokine receptors.

Propagation of embryonic stem (ES) cells with an undifferentiated pluripotential phenotype depends on leukemia inhibitory factor (LIF). The LIF receptor complex is composed of a heterodimer of LIF receptor alpha (LIFR alpha) and gp130. To activate LIFR signaling pathways independently from endogenous ones, we constructed chimeric receptors by linking the extracellular domain of human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha or beta (hGMR alpha or beta) to the transmembrane and cytoplasmic regions of either mouse LIFR alpha or gp130. hGMR alpha-mLIFR/hGMR beta-mgp130 or hGMR alpha-mgp130/hGMR beta-mgp130, but not hGMR alpha-mLIFR/hGMR beta-mLIFR, preserved the self-renewal activity in A3 ES cells. All of these chimeric receptors were phosphorylated after hGM-CSF stimulation without phosphorylation of endogenous gp130. Phosphorylation of the signal transducer and activator of transcription 3 through chimeric receptors correlated with the undifferentiated phenotype. Therefore, these chimeric receptors prove useful to analyze mechanisms of the self-renewal of ES cells.

Animals↗

PubMed1998

Specific isoprenyl group linked to transducin gamma-subunit is a determinant of its unique signaling properties among G-proteins.

Among 11 subtypes of heterotrimeric G-protein gamma-subunit, gamma1 (rod), gamma8 (cone) and gamma11 are modified with farnesyl while the others are modified with geranylgeranyl at the C-terminus. To understand the role of specific isoprenylation (farnesylation) of retinal transducin, we examined how and to what extent the type of isoprenyl group affects transducin-beta gamma (beta1 gamma1) functions such as interactions with membranes, Galpha/receptor, and effectors. To this end, the C-terminal farnesylation signal sequence (CVIS) of gamma1 was replaced by a geranylgeranylation signal (CVIL), and the resultant mutant (S74L) or wild-type (WT) gamma1 was coexpressed with beta1 in the baculovirus-Tn5 insect cell system. Both gamma1WT and gamma1S74L expressed as a beta gamma complex were mixtures modified with farnesyl and geranylgeranyl groups. The ratio of farnesyl to geranylgeranyl in preparations of beta1 gamma1WT and beta1 gamma1S74L purified from the Tn5 cell membrane fraction was about 1:2 and 1:6, respectively. These two forms of recombinant beta1 gamma1 and retinal beta1 gamma1 were different in their abilities to associate with rod outer segment membranes with the following rank order: beta1 gamma1S74L > beta1 gamma1WT > retinal beta1 gamma1. Functionally, beta1 gamma1S74L was the most potent to promote pertussis toxin-catalyzed ADP ribosylation of transducin-alpha (Talpha), to stimulate metarhodopsin II-catalyzed GTPgammaS-binding reaction to Talpha and to modulate adenylyl cyclase and phospholipase C activities. All of the beta1 gamma1 functions absolutely required the isoprenylation of the gamma-subunit. As for the interaction with Goalpha and adenylyl cyclase, predominantly geranylgeranylated beta1 gamma1S74L was less effective than geranylgeranylated beta1 gamma2 purified from bovine brain. These results demonstrate that the properties of Gbeta gamma are strongly affected by the type of functionally indispensable isoprenylation in addition to the amino acid sequence of Ggamma. The relative contribution of the two factors depends on proteins with which Gbeta gamma interacts.

Animals↗

PubMed1998

Neutrophil elastase enhances intercellular adhesion molecule-1 expression.

BACKGROUND: Elastase released from activated neutrophils is an important mediator of inflammatory tissue damage. We investigated the effect of human neutrophil elastase (NE) inhibitor (ONO-5046) on reperfusion injury after pancreaticoduodenal transplantation in rats by measuring the expression of intercellular adhesion molecule-1 (ICAM-1). Additional in vitro experiments were conducted to investigate the effect of NE on ICAM-1 mRNA transcription in a rat endothelial cell line (WK-5) and human umbilical vein endothelial cells (HUVEC). METHODS: In an in vivo experiment, male Wistar rats were transplanted with syngeneic pancreaticoduodenal grafts. An NE inhibitor, ONO-5046, was injected intravenously 5 min before vascular clamping and immediately after reperfusion at a dose of 10 mg/kg. ICAM-1 expression was determined by immunostaining and Northern analysis. In in vitro experiments, the effects of NE and chemical agents on ICAM-1 mRNA transcripts were determined in WK-5 cells and HUVEC. RESULTS: Pretreatment with ONO-5046 decreased ICAM-1 immunostaining in the pancreatic graft and inhibited the increase in ICAM-1 mRNA levels in grafts after reperfusion. ICAM-1 mRNA levels in WK-5 cells and HUVEC showed stimulation by NE, while ONO-5046 inhibited this increase. Calcium ionophore (A23187) augmented NE stimulation of ICAM-1 mRNA levels in these cells. In contrast, a phospholipase C inhibitor (U73122) blunted NE induction of ICAM-1 mRNA, and either calcium chelator (TMB-8) or a nuclear factor-kappa B inhibitor (pyrrolidine dithiocarbamate) completely inhibited induction. CONCLUSION: These results indicate that NE stimulates ICAM-1 expression in pancreatic grafts via intracellular Ca2+ influx and a phospholipase C signal transduction.

Animals↗

PubMed1998

Molecular analysis of a novel protein kinase in maturing rice seed.

Protein kinases play important roles in controlling biological functions. We employed PCR-based cloning technique to isolate a protein kinase gene from rice endosperm and obtained a novel protein kinase (REK) cDNA clone from a cDNA library constructed from maturing rice seed. The deduced amino acid sequence from the cDNA exhibited a high similarity to the wheat abscisic acid inducible protein kinase (PKABA1), including 11 conserved regions of the catalytic domain. REK belongs to the SNF1-related family that possesses abundant acidic amino acid resides in the C-terminal region. RT-PCR analysis showed that the REK gene is expressed in leaf and maturing seed, but not in stem and root. Bacterial recombinant REK showed autophosphorylation activity depending upon Ca2+. In addition, we isolated a REK genomic clone and determined its gene structure.

Amino Acid Sequence↗

PubMed1998

Novel hydrogen peroxide metabolism in suspension cells of Scutellaria baicalensis Georgi.

We identified a rapid and novel system to effectively metabolize a large amount of H2O2 in the suspension cells of Scutellaria baicalensis Georgi. In response to an elicitor, the cells immediately initiate the hydrolysis of baicalein 7-O-beta-D-glucuronide by beta-glucuronidase, and the released baicalein is then quickly oxidized to 6,7-dehydrobaicalein by peroxidases. Hydrogen peroxide is effectively consumed during the peroxidase reaction. The beta-glucuronidase inhibitor, saccharic acid 1,4-lactone, significantly reduced the H2O2-metabolizing ability of the Scutellaria cells, indicating that beta-glucuronidase, which does not catalyze the H2O2 degradation, plays an important role in the H2O2 metabolism. As H2O2-metabolizing enzymes, we purified two peroxidases using ammonium sulfate precipitation followed by sequential chromatography on CM-cellulose and hydroxylapatite. Both peroxidases show high H2O2-metabolizing activity using baicalein, whereas other endogenous flavones are not substrates of the peroxidase reaction. Therefore, baicalein predominantly contributed to H2O2 metabolism. Because beta-glucuronidase, cell wall peroxidases, and baicalein pre-exist in Scutellaria cells, their constitutive presence enables the cells to rapidly induce the H2O2-metabolizing system.

Cell Wall↗

PubMed1998

Cloning and characterization of the mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene.

The gene encoding the mouse precursor of pituitary adenylate cyclase-activating polypeptide (PACAP) has been cloned, and its structural organization was determined. Using the 5'-rapid amplification of cDNA ends (RACE) procedure, three types of transcription initiation produced by alternative exon usage of two untranslated alternative exons (exons 1A and 1B) were defined. The PACAP gene spans 6.6kb of genomic DNA and is composed of six exons including the alternative exons. The signal peptide, PACAP-related peptide and mature 38-amino acid PACAP (PACAP-38) are encoded within exons 2, 4 and 5, respectively. The 5'-flanking region of the PACAP gene contains several sequence motifs homologous to cAMP response element, TPA response element, and growth hormone factor-1 binding site. A dinucleotide repeat sequence is present in an intron. In addition, there are di- and tetranucleotide repeat sequences 2.4kb and 3.2kb upstream to the translation start point, respectively. The overall intron-exon organization and the production of the alternate mRNAs of the PACAP gene are markedly similar to those of the growth hormone-releasing hormone (GHRH), supporting the hypothesis that the two genes encoding GHRH or PACAP were originated from a gene duplication. Promoter analysis of the 5'-flanking region of the PACAP gene using a luciferase gene reporter system revealed that the isolated 5'-flanking region has functional promoter activity and is responsible for inducible expression.

Alternative Splicing↗

PubMed1998

Protein-bound acrolein: potential markers for oxidative stress.

Acrolein (CH2==CH---CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress. To verify the presence of protein-bound acrolein in vivo, the mAb (mAb5F6) against the acrolein-modified keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine adduct, Nepsilon-(3-formyl-3, 4-dehydropiperidino)lysine, constitutes an epitope of the antibody. Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cells and the thickening neointima of arterial walls. The observations that (i) oxidative modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein. These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and long-term damage to protein in aging, atherosclerosis, and diabetes.

Acrolein↗

PubMed1998

Specific tandem GG to TT base substitutions induced by acetaldehyde are due to intra-strand crosslinks between adjacent guanine bases.

Acetaldehyde is present in tobacco smoke and automotive exhaust gases, is produced by the oxidation of ethanol, and causes respiratory organ cancers in animals. We show both the types and spectra of acetaldehyde-induced mutations in supF genes in double- and single-stranded shuttle vector plasmids replicated in human cells. Of the 101 mutants obtained from the double-stranded plasmids, 63% had tandem base substitutions, of which the predominant type is GG to TT transversions. Of the 44 mutants obtained from the single-stranded plasmids, 39% had tandem mutations that are of a different type than the double-stranded ones. The GG to TT tandem substitutions could arise from intra-strand crosslinks. Our data indicate that acetaldehyde forms intra- as well as inter-strand crosslinks between adjacent two-guanine bases. Based upon the following observations: XP-A protein binds to acetaldehyde-treated DNA, DNA excision repair-deficient xeroderma pigmentosum (XP) cells were more sensitive to acetaldehyde than the repair-proficient normal cells, and a higher frequency of acetaldehyde-induced mutations of the shuttle vectors was found in XP cells than in normal cells, we propose that the DNA damage caused by acetaldehyde is removed by the nucleotide excision repair pathway. Since treatment with acetaldehyde yields very specific GG to TT tandem base substitutions in DNA, such changes can be used as a probe to identify acetaldehyde as the causal agent in human tumors.

Acetaldehyde↗