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L K Tay

Publications and source records attributed to L K Tay.

35 records · Page 2Linked to original sources
PubMed1985

Effect of human chorionic gonadotrophin on 7,12-dimethylbenz[a]anthracene-induced DNA binding and repair synthesis by rat mammary epithelial cells.

The administration of the placental hormone human chorionic gonadotrophin (HCG) to 50-day-old virgin Sprague--Dawley rats has been shown to reduce the incidence of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary cancer. We now report from studies using rat mammary epithelial cells in culture that the anti-carcinogenic effect of HCG may be related to its effect on DNA binding of DMBA and on DNA repair. The results showed that the level of excision repair in cells derived from young virgin (YV) rats grown in the presence of HCG (10 units/ml) was 2.5-4.0 times higher than the level exhibited by control YV cells and 1.5-2.5 times over that obtained for cells from old virgin and parous rats. The effect of HCG on DMBA-DNA binding was also determined in YV cells cultured in the presence of HCG (10 units/ml). Results from this study indicated that DMBA-DNA binding was inhibited by 30-40% in HCG-treated cells as compared to control cells. DNA binding of DMBA was also determined with mammary epithelial cells from YV rats which were given subcutaneous injections of HCG (5 units/rat) 5 times per week for 4 weeks. Using this in vivo-in vitro protocol, DMBA-DNA binding was 17-51% lower in cells from HCG-treated rats than in cells derived from control saline-treated rats. These results suggest that the protective effect provided by HCG against DMBA-induced mammary tumorigenesis may be attributed to its ability to inhibit binding of the carcinogen to mammary cell DNA and to its ability to increase the level of excision repair in the cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

In vitro metabolism of 7,12-dimethylbenz[a]anthracene in mammary epithelial cells from rats with different susceptibilities to carcinogenesis.

These in vitro metabolism studies of 7,12-dimethylbenz[a]anthracene (DMBA) by rat mammary epithelial cells were initiated to determine whether differences in the incidence of DMBA-induced mammary carcinomas observed between young virgin, old virgin and parous Sprague-Dawley rats can be explained through variations in their ability to metabolize DMBA. The results show that: (a) qualitatively, the metabolic profiles produced by epithelial cells from the 3 groups of rats were similar; (b) the level of metabolism with cells from young virgin and parous rats was similar but was 1.5-2.0 times higher than that obtained with cells from old virgin rats; c) the major ethyl acetate-soluble metabolite detected by h.p.l.c. from cells of old virgin and parous rats was the trans-8,9-dihydrodiol (50-65% of total metabolites), whereas the majority of the radioactivity following incubation with cells from young virgin rats co-eluted with very polar metabolites (65% of total metabolites); and (d) the amount of phenolic metabolites produced by young virgin rat cells was higher than in old virgin or parous rat cells. The data suggest that the susceptibility of young virgin rat mammary cells to DMBA may be due in part to the conversion of a greater percentage of DMBA to phenolic compounds and to water- and ethyl acetate-soluble polar metabolites, and event known to influence the susceptibility of cultured cells to the cytotoxic effects of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Molecular and cellular basis of the mammary gland susceptibility to carcinogenesis.

Mammary carcinomas induced by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) to young virgin rats arise from undifferentiated terminal ductal structures called terminal end buds (TEBs). TEBs that normally differentiate into alveolar buds (ABs) and lobules under the influence of DMBA develop intraductal proliferations which progress to carcinoma. The high susceptibility of the young virgin rat TEBs to neoplastic transformation is due to its large proliferative compartment, with cells cycling every 10 hr, and to a higher (3)H-DMBA uptake. Progressive differentiation of TEBs into ABs and lobules or their regression to terminal ducts (TDs) is seen with aging. Complete differentiation of the gland is attained only through pregnancy and lactation. The greater differentiation of the gland is manifested as permanent structural changes, consisting in the disappearance of TEBs and in a diminution of the number of TDs due to their differentiation into ABs and lobules. This greater differentiation results in a diminished or total refractoriness of the gland to the carcinogen because ABs and lobules have a lower proliferative compartment and a longer cell cycle than TEBs and TDs. Cells of parous rats have both in vivo and in vitro a lower DMBA-DNA binding capacity, a lower DNA synthesis and a greater ability to repair DMBA damaged DNA than cells of young virgin rats. The more efficient DNA repair capacity of the parous rat mammary gland is demonstrated by the induction of unscheduled DNA synthesis and a removal of DMBA-DNA adducts.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Differentiation of the mammary gland and susceptibility to carcinogenesis.

It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

7,12-dimethylbenz[a]anthracene-induced DNA binding and repair synthesis in susceptible and nonsusceptible mammary epithelial cells in culture.

The effect of age and parity on the binding of 7,12-dimethybenz[a]anthracene (DMBA) to DNA and the repair of DMBA-damaged DNA have been demonstrated in logarithmic phase and confluent mammary epithelial cell cultures from young virgin (YV), old virgin (OV), and parous (P) noninbred and inbred Sprague-Dawley rats. Over a dose range of 0.1-0.4 micrograms DMBA/ml, DNA binding was 1.5-to 2.0-fold higher in YV cells than in OV or P cells. In addition, a steeper slope of the dose-response curve was obtained with YV cells, suggesting a greater susceptibility of YV cells to DMBA. Excision repair was determined by measuring, in the presence of hydroxyurea and 5-bromodeoxyuridine, tritiated thymidine incorporation into DNA during the repair process. At high doses od DMBA (0.5-2.0 micrograms/ml), excision repair in YV cells was 1.5 times higher than in OV cells and 2 times higher than in P cells. However, with lower DMBA doses (less than 0.5 micrograms/ml) similar levels of repair were obtained in all 3 groups of rats. Since binding to DNA is higher in YV cells at these low DMBA doses, ti is apparent that OV and P cells exhibit a greater DNA repair per unit damage. These results, therefore, suggest that age and parity not only lower the binding of DMBA to mammary epithelial cell DNA but also increase the efficiency of DNA repair processes, which may explain the lower susceptibility of OV and P rats to DMBA-induced mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Binding of 6-hydroxymethylbenzo[a]pyrene and 6-acetoxymethylbenzo[a]pyrene to DNA.

The carcinogenic hydrocarbons 6-hydroxymethylbenzo[a]pyrene (6-HOCH2-B[a]P) and 6-acetoxymethylbenzo[a]pyrene (6-AcOCH2-B[a]P) were examined for their ability to bind to rat and calf thymus DNA. The data indicate there are no appreciable differences in the amount of binding to the two types of DNA. Non-enzymatic binding of 6-HOCH2-B[a]P was low (5 mumol hydrocarbon/mol DNA P) but 6-AcOCH2-B[a]P was bound to a considerable extent (88.4--97.3 mumol hydrocarbon/mol DNA P). Non-enzymatic binding of 6-HOCH2-B[a]P was greatly increased in the presence of ATP. Binding of 6-HOCH2-B[a]P in the presence of liver microsomes from untreated rats or from rats pretreated with 3-methylcholanthrene (3-MC) never exceeded 5 mumol hydrocarbon/mol DNA P. Binding of 6-HOCH2-B[a]P in the presence of a PAPS generating system was less than non-enzymatic binding mediated by ATP and was dependent on the presence of ATP rather than ATP and sulfate. Binding was reduced by 50% when ADP was employed in the non-enzymatic reaction and was negligible in the presence of AMP or adenosine, indicating that a diphosphate group is necessary. Incubation of 6-HOCH2-B[a]P with DNA in the presence of ATP, CTP, GTP, or UTP showed that ATP was the most effective mediator of the binding reaction. These observations suggest that 6-HOCH2-B[a]P is converted to a phosphate ester which, like 6-AcOCH2-B[a]P, is much more reactive than 6-HOCH2-B[a]P itself.

Adenine Nucleotides↗
PubMed1978

Viruses and bacteria associated with acute respiratory illnesses in young children in general practice.

The results obtained and the laboratory methods used for the isolation of viruses and bacteria from Malaysian children with acute respiratory illnesses seen in a private clinic are described. Of the 65 children studied virus isolations were obtained from 26 children, bacteria from 10 and both virus and bacteria from another 5. The agents isolated were influenza viruses, parainfluenza viruses, adenoviruses, Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus pyogenes.

Acute Disease↗
PubMed1978

Reactions of the carcinogens 7-hydroxymethyl-12-methylbenz(A)anthracene and 7-acetoxymethyl-12-methylbenz(A)anthracene with DNA.

The carcinogen 7-hydroxymethyl-12-methylbenz(a)anthracene reacts very poorly with DNA (2 mumoles hydrocarbon/mole DNA P) in the absence of enzymes whereas the carcinogen 7-acetoxymethyl-12-methylbenz(a)-anthracene reacts readily with DNA (21.4 mumoles hydrocarbon/mole DNA DNA P). The high reactivity of the acetoxymethyl compound suggests it functions as an ultimate carcinogen whereas the low reactivity of the hydroxymethyl compound suggests that it requires further mebabolism to a reactive ester (e.g. sulfate) before it becomes an ultimate carcinogen. To test this hypothesis tritium labeled 7-hydroxymethyl-12-methylbenz(a)anthracene was synthesized and reaction with calf thymus DNA studied in the presence and absence of a PAPS generating system. The results demonstrate that in the absence of a PAPS generating system and ATP, virtually no reaction with DNA could be detected. However, in the presence of the complete system, the radioactivity associated with phenol-extracted ethanol precipitated DNA was 27.5 mumoles of hydrocarbon/mole DNA P. The reaction with DNA was shown to be only partially dependent on sulfate ion which when omitted from the reaction mixture gave 22.7 mumoles of hydrocarbon/mole DNA P, whereas if ATP were omitted, no reaction occurred (0.4 mumoles/mole DNA P). However, if enzyme is omitted from the system, reaction occurs in the presence (44.8 mumoles/mole DNA P), but not in the absence of ATP. These data demonstrate that ATP mediates the reaction of this hydrocarbon with DNA, suggesting the formation of a reactive phosphate ester.

Adenine Nucleotides↗
PubMed1975

Septicaemia from prolonged intravenous infusions.

Four cases of septicaemia in children were traced to contaminated intravenous infusions and volume control sets. In each case Pseudomonas cepacia was isolated from multiple blood cultures and from intravenous fluid within the volume control set. The first patient died of septicaemia after a long and complicated postoperative period. The other three patients received appropriate antibiotics after removal of the contaminated intravenous sets and they recovered within 2 weeks.

Ampicillin↗
PubMedDate not supplied

A report on three patients with "rapid cycling" unipolar depression.

We report three cases of unipolar depression who meet criteria for "rapid cycling" by having four or more major depressive episodes within a 1-year period. This report describes the clinical characteristics of the three patients and discusses the concept of false unipolar depression, and compares these patients with the "pseudounipolar" group described by Akiskal et al. Our findings support the clinical notion that rapid cycling in unipolar depression is a rarity.

Adult↗
PubMedDate not supplied

Diagnostic reliability of the history of hypomania in bipolar II patients and patients with major depression.

Records of patients who had been systematically evaluated at the Center for Anxiety and Depression were reviewed. Included in this report are records of patients who had a diagnosis of bipolar II or unipolar affective disorder as determined by one of the authors and who also underwent a Structured Clinical Interview for DSM-III (SCID). A second study was undertaken with L.K.T. observing the clinical interview of D.L.D. and both clinicians making a diagnosis for the patient. There was reasonable diagnostic agreement between D.L.D. and the SCID for diagnosis of bipolar II disorder. Twelve of 34 patients clinically diagnosed as bipolar II were diagnosed by the SCID as unipolar. These 12 patients failed to demonstrate clinical factors, which could help explain the diagnostic difference between SCID and the clinical diagnosis. There was excellent agreement on 34 patients as to the presence or absence of hypomania, comparing two clinicians. The SCID interview underestimates the diagnosis of hypomania, a condition that can be diagnosed reliably by clinicians trained to make this diagnosis. This finding has some implications for DSM-IV, where there is a proposal for inclusion of bipolar II disorder as a parallel entity with bipolar disorder.

Adult↗
PubMedDate not supplied

Metabolism of trans-stilbene in rabbits and rats.

The biotransformation of intramuscularly administered 14C-labeled trans-stilbene was investigated in both rabbits and rats. In rabbits radioactivity was excreted (78.8% in 17 days) almost exclusively in the urine. In rats, feces accounted for more than half of the total excretion (80.3% in 19 days). Hydroxylated metabolites in urine and feces were identified by thin-layer chromatography and quantitated by liquid scintillation counting. They were 4-hydroxy and 4,4'-dihydroxystilbene, and the two monomethyl ethers of 3,4-dihydroxystilbene and 4,4'-dihydroxybibenzyl. In addition, four polyhydroxylated metabolites of stilbene and bibenzyl were identified in rat urine by comparison of gas-liquid chromatography retention times of their silyl derivatives with synthetic reference compounds. They were 3,4,4'-trihydroxystilbene, and 3,4-dihydroxy-, 3,4,4'=trihydroxy-, and 3,4,3',4'-tetrahydroxybibenzyl. Oxidative cleavage of trans-stilbene to benzoic acid and 4-hydroxy- and 3,4-dihydroxybenzoic acid was established by the presence of both the free acids and conjugates of these compounds in both rabbit and rat urine. Their glycine conjugates were identified by thin-layer chromatography and quantitated by reverse isotope dilution procedures from unhydrolyzed rabbit and rat urine. Percentages obtained indicate that cleavage of trans-stilbene is more extensive in rabbits (9.5%) than in rats (2.7%).

Animals↗