Biomedical subjects

J K Lin

Publications and source records attributed to J K Lin.

At least 145 records · Page 8Linked to original sources

PubMed1993

Penta-acetyl geniposide inhibits the growth and development of C-6 glioma cells in rats.

Experimental data are provided which demonstrate the inhibitory effects of penta-acetyl geniposide, (Ac)5-GP, on the growth and development of C-6 glioma cells inoculated into rats. In the pretreatment experiments, (Ac)5-GP prolonged the latency period of T50 (time for 50% tumour incidence). At week 7, the growth inhibition was 41% with 5 mg/kg and 75% with 10 mg/kg of (Ac)5-GP. In the post-treatment experiments, growth inhibition was less. No significant hepatotoxic effects were observed in the treated group, indicated by the constant levels of serum enzymes (e.g. asparate aminotransferase). We suggest that (Ac)5-GP is a potent chemopreventive agent on glioma cells.

Animals↗

PubMed1993

Relaxation of rat thoracic aorta by N-nitroso compounds and nitroprusside and their modifications of nucleic acid bases through release of nitric oxide.

Nitroprusside and two newly synthesized direct-acting mutagens, N-nitroso-2-fluorenylactamide and N-nitroso-dinitroacetaminophen, were able to elicit the concentration-dependent relaxation of rat aorta. The vascular responses could be antagonized by hemoglobin that binds nitric oxide with high affinity and by methylene blue which inhibits soluble guanylate cyclase activity. We used four bases in DNA as the substrates to test the capacity to deaminate of the two compounds. Xanthine, hypoxanthine and uracil as well as some unusual bases such as 8-OH-adenine and 8-OH-guanine were found. These findings suggest that both the muscle relaxation and mutagenicity of these two compounds might be due to the release of nitric oxide in living cells.

2-Acetylaminofluorene↗

PubMed1993

The genotoxicity of the waste water discharged from paraquat manufacturing and its pyridyl components.

The genotoxic potencies of waste water condensate from paraquat manufacturing and its pyridyl components on V79 cells were evaluated using the alkaline elution assay and 6-thioguanine resistance mutation assay. Although 2,2'-dipyridyl and 2,2',2"-tripyridyl both were highly cytotoxic to the cells, only 2,2'-dipyridyl induced moderate DNA-cleaving activity and a low frequency of thioguanine resistance mutation in V79 cells. However, equally toxic doses of waste water condensate exhibited highly DNA-damaging and mutagenic activities in the same cell system. After chelation of ferrous ions, the number of DNA lesions and frequency of 6-TGr mutations induced by waste water condensate were slightly suppressed, whereas by contrast those induced by 2,2'-dipyridyl were significantly potentiated. These results indicate that the coordination compound formation of pyridyl derivatives of waste water with metal ions, especially ferrous ions, in biological systems may be closely related to these genotoxic mechanisms. Finally, it was found that DMSO (a scavenger of hydroxyl radical) and catalase could remarkably protect cells from genotoxic damage induced by waste water condensate, 2,2'-dipyridyl and their ferrous complexes, but this protection was not observed in cells which were treated with SOD (superoxide dismutase). This suggests that the generation of some unknown active oxygen species may be involved in the genotoxic mechanisms of waste water condensate and its constituent 2,2'-dipyridyl.

2,2'-Dipyridyl↗

PubMed1993

Inhibition of 8-hydroxydeoxyguanosine formation by curcumin in mouse fibroblast cells.

Curcumin, a pigment responsible for the yellow color of curry, has been shown to be an anti-inflammation agent, an antioxidant and an antipromoter. 8-Hydroxydeoxyguanosine (8-OH-dG), an oxidized nucleoside, may be responsible for a genetic event of tumor promotion in carcinogenesis. 8-OH-dG can be detected selectively and sensitively at the fmol level by HPLC-electrochemical detection at an applied potential of +0.8 V versus Ag/AgCl. Phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces lipid peroxidation and 8-OH-dG formation. Curcumin can strongly scavenge the hydroxyl radical (OH.) to prevent 8-OH-dG formation from dG (deoxyguanosine) in vitro and reduce the production of PMA-induced lipid peroxidation and 8-OH-dG in mouse fibroblast cells. These results suggest that curcumin inhibits the PMA-induced tumor promotion by functioning as an OH. radical scavenger to prevent 8-OH-dG formation within the DNA molecule.

3T3 Cells↗

PubMed1993

Inhibitory effects of curcumin on protein kinase C activity induced by 12-O-tetradecanoyl-phorbol-13-acetate in NIH 3T3 cells.

Curcumin is a dietary pigment responsible for the yellow color of curry. It is a potent inhibitor of tumor promotion induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse skin. When mouse fibroblast cells (NIH 3T3) were treated with TPA alone, protein kinase C (PKC) translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 microns curcumin for 15 min inhibited TPA-induced PKC activity in particulate fraction by 26 or 60% and did not affect the level of PKC protein. Curcumin also inhibited PKC activity in both cytosolic and particulate fractions in vitro by competing with phosphatidylserine. However, the inhibitory effect of curcumin was reduced after preincubation with the thiol compounds. These findings suggest that the suppression of PKC activity may contribute to the molecular mechanism of inhibition of TPA-induced tumor promotion by curcumin.

3T3 Cells↗

PubMed1993

[Psychogenic dizziness].

Psychogenic dizziness is defined as recurring or persistent symptoms of balance dysfunction, inconsistent with organic vestibular disease as determined by history, clinical examination and pertinent investigations, and consistent with emotional origin. Of 1,335 patients seen in our dizziness clinic between January 1988 and August 1991, psychogenic dizziness was diagnosed in 180 (13.5%) patients. There were 67 men and 113 women aged from 12 to 77 years (mean age 40.2 years). The characteristics of psychogenic dizziness are: (1) continuous dizziness for long periods of time; (2) younger patients; (3) predominant female; (4) associated symptoms of panic attack, such as headache, breathlessness, nausea, sleep disturbance, paresthesias, anxiety and palpitation; (5) symptoms of aggravation due to stressful life events; (6) normal neurotological bedside examination; (7) hyperventilation reproduced accurately. The electronystagmographic results of 74 patients show normal bithermal caloric responses in 47 patients (63.5%), caloric hyperactivity in 21 patients (28.4%), canal paresis in four patients (5.4%), canal paresis with directional preponderance in two patients (2.7%), large random voluntary eye swings or severe blinking in 35 patients (47.3%), and spontaneous nystagmus (slow phase velocity < 6.5 degrees/s) in four patients (5.4%). There were 31 patients who consulted psychiatrists with diagnoses of anxiety (51.6%), depression (16.1%), insomnia (12.9%), psychosomatic disorder and adjustment disorder. Treatment of patients with psychogenic dizziness must be directed at the underlying anxiety. Psychiatric consultation is necessary.

Adolescent↗

PubMed1992

Genotoxicities of nitropyrenes and their modulation by apigenin, tannic acid, ellagic acid and indole-3-carbinol in the Salmonella and CHO systems.

Four naturally occurring compounds, indole-3-carbinol (I3C), apigenin (Api), ellagic acid (EA) and tannic acid (TA), were tested for their inhibitory effects against 1-nitropyrene- (1-NP) or 1,6-dinitropyrene (1,6-DNP)-induced genotoxicity in Salmonella tester strains and Chinese hamster ovary (CHO) cells. Api and TA strongly inhibited the bacterial mutagenesis induced by nitropyrenes, while I3C and EA had little or no effect. For example, in TA98, 0.2 mumole Api resulted in 48% and 56% inhibition of the mutagenicity induced by 4 nmole 1-NP and 0.035 nmole 1,6-DNP, respectively. With an equal dose, TA caused 46% and 50% reduction of the mutagenicity induced by 1-NP and 1,6-DNP, respectively. As expected, a good correlation was observed between the antimutagenicity of nitropyrenes and their inhibitory effect on nitroreductase activity. This indicated that one of the possible antimutagenic mechanisms of Api or TA was to inactivate the metabolism of nitropyrenes. Two biological end-points, cytotoxicity and sister-chromatid exchange (SCEs), were used to screen the antigenotoxic effects of these compounds in CHO cells. At the sub-cytotoxic dose, I3C, Api and TA all protected against the cytotoxicity induced by 1-NP and 1,6-DNP, but only TA and Api gave a significant reduction of the frequency of SCEs. Moreover, this reduction was found to be highly dose-dependent.

Animals↗

PubMed1992

In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor beta 1.

The effect of transforming growth factor beta 1 (TGF-beta 1) on human hepatoma cells (Hep 3B) was studied. Cell death was observed when the serum starved Hep 3B cells were exposed to a very low concentration of TGF-beta 1. The half-maximal cytocidal concentration of TGF-beta 1 was around 20 pM. Cell death began approximately 24 h following treatment, with more than 80% of the cells dying after 48 h. In contrast, the control cells, which were cultured in serum-free condition, still gradually proliferated. Furthermore, the cytocidal effect of TGF-beta 1 on Hep 3B cells was not altered by either cycloheximide or actinomycin D. It was discovered, using diphenylamine assay, that TGF-beta 1 induced DNA fragmentation in Hep 3B cells. Using gel electrophoresis, the fragmented DNA could be displayed, and showed a characteristic stepladder pattern. Thus, it appeared that TGF-beta 1 induced a particular pathway in Hep 3B cells in which de novo protein synthesis was not actively involved, but endogenous nuclease was activated which cleaves cellular DNA and induces cell death.

Carcinoma, Hepatocellular↗

PubMed1992

Trend of large bowel tuberculosis and the relation with pulmonary tuberculosis.

From 1965 to 1989, 60 cases of large bowel tuberculosis among 116 cases of abdominal tuberculosis are reviewed and analyzed. Lesions located in the cecum or ileocecal region were found in 49 of the 60 cases. Most of the patients (50/60) received surgical intervention, but the definite diagnoses had never been proved until surgery. The diagnoses were proved by histopathologic examination in these 50 cases. Antituberculosis medications were given for at least nine months in all patients. Twenty-nine of the 50 patients who received operations had primary anastomosis during the operations, and no leakage occurred. Evidence of pulmonary tuberculous lesions could be found in 40 of the 60 cases. Positive findings of tubercle bacilli in sputum smear or culture were noted in 13 cases. The positive rate of sputum examinations decreased during 1980 to 1989; 25.6 percent (10/39) were positive from 1965 to 1979 and 14 percent (3/21) were positive from 1980 to 1989. In the meantime, there was a steady decline in the cases of large bowel tuberculosis in the most recent few years. An antituberculosis program has been carried out in the past 40 years with remarkable effect in the Taiwan area, but the possibility of intestinal tuberculosis still exists. The authors suggest that surgeons keep tuberculosis in mind when they are dealing with patients who suffer from intestinal obstruction of unknown origin with the suspected findings of pulmonary tuberculosis in chest x-ray films.

Adolescent↗

PubMed1992

Chromosomal aberrations and sister-chromatid exchanges induced by N-nitroso-2-acetylaminofluorene and their modifications by arsenite and selenite in Chinese hamster ovary cells.

The frequencies of chromosomal aberrations (CA) and sister-chromatid exchanges (SCE) in Chinese hamster cells were significantly increased by the direct-acting mutagen N-nitroso-2-acetylaminofluorene (N-NO-AAF) at the concentration of 0.1 mM. N-NO-AAF was prepared by nitrosation of the protohepatocarcinogen 2-acetylaminofluorene. The induced CA, which included chromatid breaks, chromatid exchanges, chromosome breaks, and chromosome ring formation were significantly potentiated by the presence of sodium arsenite (10 microM), but not by hydroxyurea (20 mM) or cytosine arabinoside (25 microM). On the other hand, the clastogenic effect of N-NO-AAF was effectively inhibited by sodium selenite (100 microM). Arsenite (10 microM) was shown to be moderately active in CA induction which was partially blocked by the presence of selenite (10 nM). N-Nitroso compounds such as N-nitroso-N-methylurea, N-nitroso-N-ethylurea and N-methyl-N'-nitro-N-nitrosoguanidine were equally or more active in the induction of CA and SCE in CHO cells when compared with N-NO-AAF. The cell cycle was significantly delayed by the intervention of N-NO-AAF.

2-Acetylaminofluorene↗

PubMed1992

Enhancement of the mutagenicity of polyphenols by chlorination and nitrosation in Salmonella typhimurium.

The hydrolytic products of lignins, humic acids and industrial waste including hydroquinone, catechol, resorcinol, pyrogallol and 1,2,4-benzenetriol are widely distributed in water sources. These polyphenols can interact with chlorine or nitrite to yield new derivatives. Generally, these new products possess more mutagenic potential than their original compounds. Furthermore, the mutagenicity of these polyphenols and their derivatives can be dramatically reduced by rodent liver microsomal enzymes (S9). The mutagenicity of polyphenols is in this order: hydroquinone greater than 1,2,4-benzenetriol greater than pyrogallol, while catechol, resorcinol and phloroglucinol are non-mutagenic. The ultimate product of chlorination or nitrosation of hydroquinone has been identified to be p-benzoquinone. The formation of active oxygen species including superoxide anion and hydrogen peroxide by polyphenols has been demonstrated and this may contribute partly to the molecular mechanisms of polyphenol mutagenicity.

Catechols↗

PubMed1992

Hepatotoxicity and hepatocarcinogenicity in rats fed squid with or without exogenous nitrite.

The popular seafood squid contains high levels of naturally occurring amines such as dimethylamine (DMA) trimethylamine and trimethylamine-N-oxide (TMAO). The hepatotoxicity and hepatocarcinogenicity of squid with or without exogenous nitrite were investigated in rats. Acute necrosis including polymorphogenic neutrophil infiltration, haemorrhage and cholangiofibrosis were observed in the livers of most rats fed squid. Hepatocellular carcinoma (HCC) was induced in two out of 12 rats (16%) by feeding 10% squid in Purina rat chow for 10 months. The incidence of HCC was increased to four out of 10 rats (33%) when 0.3% NaNO2 was added to the above diet. At the end of the experiment a marked elevation of serum gamma-glutamate transferase was observed in treated groups, but no significant changes in the activities of serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were detected. Vitamin C (0.3%) gave partial protection against hepatic damage. The concentration of DMA in squid is estimated to be 0.19%; this concentration did not induce HCC under the experimental conditions used. Therefore it is suggested that another major naturally occurring amine in squid, TMAO, could be one of the important factors involved in the induction of hepatotoxicity and hepatocarcinogenicity in rats.

Animals↗

PubMed1992

Enhancement of the mutagenicity of IQ and MeIQ by nitrite in the Salmonella system.

The fried food mutagens IQ, MeIQ, Glu-P-1 and Trp-P-2 were treated with nitrite at pH 3.0 for 1 h at 37 degrees C. The resulting reaction mixtures were tested for mutagenicity towards Salmonella typhimurium TA97, TA98, TA100 and TA1535. Glu-P-1 and Trp-P-2 were readily converted to weak or non-mutagenic deaminated compounds, whereas IQ and MeIQ were converted to extremely strong mutagenic derivatives in both the presence and the absence of rat liver S9 mix. The mutagenicity of MeIQ in TA98 was enhanced by nitrite up to 3-fold, while that of nitrosated MeIQ was further enhanced by S9 mix up to 15-fold. The nitrosation products of MeIQ were resolved into 7 bands by TLC on silica gel plate. Bands I, III, V and VI were highly mutagenic to both TA98 and TA100. The experimental results suggest that the non-enzymatic formation of direct-acting mutagens from indirect-acting mutagens such as IQ or MeIQ might be physiologically important, especially with regard to the etiology of human gastrointestinal tract tumors.

Amines↗

PubMed1992

Biotransformation of butachlor through mercapturic acid pathway in rat tissue homogenates.

The metabolism of butachlor was studied in rat liver and kidney homogenates. In vitro incubation of butachlor with liver fractions (S9, microsome, and cytosolic fractions) formed a considerable amount of butachlor glutathione conjugate (BGSC), while the conjugating activity was not efficient for the kidney S9 fraction. There is a sex difference in the distribution of glutathione S-transferase in the liver. It seems that more enzyme activity is detected in the female liver microsome, while this is not the case in its cytosolic fraction. Further biotransformation of BGSC to mercapturate was not observed in the liver S9 fraction. This metabolite was further transformed to butachlor acetyl cysteine conjugate (BACC) in the presence of acetyl CoA, but to butachlor cysteine conjugate (BCC) in the absence of acetyl CoA. These findings demonstrated that butachlor is initially conjugated with GSH to form BGSC by the enzyme glutathione S-transferase in the liver. This metabolite is apparently transported to the kidneys, where it is transformed to the mercapturate.

Acetanilides↗

PubMed1992

Biochemical and morphological alterations in the lungs and livers of mice following exposure to polluted air in a traffic tunnel.

The air in the Lin-Shen tunnel in Taipei is heavily polluted due to heavy traffic. To elucidate the biologic effects of air pollution, we studied the biochemical alterations of Polycyclic aromatic hydrocarbons metabolic enzymes and histological changes in the livers and lungs in experimental mice under long-term and short-term exposure to the tunnel air. The concentrations of 16 Polycyclic aromatic hydrocarbons in the air were measured by HPLC, and the mutagenicity of the extract of air particulates was assayed by the Ames test. We found that the benzo(a)pyrene hydroxylase and cytochrome P-450 in the livers and nitroreductase in the lungs of the 30-day exposed animals were significantly increased as compared to the unexposed control (p < 0.005). The nitroreductase in the liver also increased but not significantly. The lungs of long-term (6 mo.) exposed mice showed anthracosis, chronic inflammation, and emphysema (10/10). The livers of the experimental animals did not show significant alteration. A whitish circular nodule appeared on the liver surface of one mouse (1/10). Microscopically, the nodule showed necrosis and hyperchromatic cells around the central vein. It is concluded that the polluted air in the traffic tunnel has evident biohazardous effects on the lungs and livers of mice under the experimental conditions.

Air Pollutants↗

PubMed1992

Differential induction of c-fos and c-jun proto-oncogenes and AP-1 activity by tumor promoter 12-O-tetradecanoyl phorbol 13-acetate in cells at different stages of tumor promotion in vitro.

A two-stage (initiation and promotion) model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the molecular mechanisms of tumor promotion in vitro. C3H10T1/2 cells which had been initiated with a subcarcinogenic dose (0.5 micrograms ml-1) of benzo[a]pyrene (B[a]P) were isolated after 12-O-tetradecanoyl phorbol 13-acetate (TPA) treatment lasting 12, 24 or 36 days. These series of partially promoted cells were designated T-12, T-24 and T-36 cells. T-12 and T-24 cells exhibited higher anchorage-independent growth on soft agar in the presence of TPA than did the initiated or T-36 cells. Cytosolic protein kinase C (PKC) in the resting state was slightly depleted in T-24 and T-36 cells. Proteolytic down-regulation of membrane-bound PKC was enhanced in T-12 cells compared with the initiated cells after 3 h of TPA treatment. Induction of c-fos and c-jun proto-oncogene expression increased two- to threefold in T-12 cells. Moreover, the basal level of c-fos mRNA progressively increased in T-12, T-24 and T-36 cells. As compared with other cell types, T-12 cells had the highest AP-1 DNA-binding activity at both the basal level and at 30 min after TPA treatment. These results indicate that deregulation of the TPA-induced cellular responses occurs in the cells at various stages of tumor promotion, and might be associated with transforming processes.

Animals↗

PubMed1991

Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells.

Curcumin, a dietary pigment responsible for the yellow color of curry, is a potent inhibitor of tumor promotion by phorbol esters. Functional activation of transcriptional factor c-Jun/AP-1 is believed to play an important role in signal transduction of phorbol 12-myristate 13-acetate-induced tumor promotion. Suppression of the c-Jun/AP-1 activation by curcumin is observed in mouse fibroblast cells. In vitro experiments indicate that inhibition of c-Jun/AP-1 binding to its cognate motif by curcumin may be responsible for the inhibition of c-Jun/AP-1-mediated gene expression. These findings show that the effect of curcumin on phorbol 12-myristate 13-acetate-induced inflammation/tumor promotion could be studied at the molecular level.

Animals↗

PubMed1991

Modulatory effect of crocetin on aflatoxin B1 cytotoxicity and DNA adduct formation in C3H10T1/2 fibroblast cell.

Crocetin is a carotenoid isolated from the seeds of Cape jasmine (Gardenia jasminoides). The cytotoxicity and DNA-adduct formation of rat microsome-activated aflatoxin B1 (AFB1) in the C3H10T1/2 cells were significantly inhibited by pretreatment of crocetin. Most significant inhibition was found at the time of 9 h after crocetin pretreatment. Under these experimental conditions, consistent elevation in the cytosolic glutathione (GSH) levels and the activities of GSH S-transferase (GST) and GSH-peroxidase (GSH-Px) were observed. Crocetin treatment also resulted in a decrease in AFB1-DNA adduct formation in vitro, while no effect of crocetin on the formation of AFB1-8,9-oxide in vitro system was detected as measured by the Trisdiol method. From these results, we suggested that the protective effect of crocetin on the AFB1-cytotoxicity in C3H10T1/2 cells might be due to the cellular defense mechanisms that elevated the cytosol GSH and the activities of GST and GSH-Px.

Aflatoxin B1↗