Reductive activation of N-oxides to cause DNA strand breakage in cell lines in vitro.
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Biomedical subjects
Publications and source records attributed to A Cahill.
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The cellular and microsomal reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) was studied aerobically and anaerobically in rat (JB1, BL8, Walker) mouse (3T3) and human (HepG2) derived cell lines. In all cases rates or reduction to the mono-N-oxide (SR 4317) were greater under anaerobic than aerobic conditions when determined using HPLC with UV and fluorescence detection. Of the rat derived cells, a transformed liver epithelial line (JB1) showed the greatest cellular and microsomal rates of reduction while Walker 256 carcinoma cells showed the lowest. Microsomal reduction of SR 4233 was the highest in preparations from rat liver but carbon monoxide did not inhibit the reaction, suggesting cytochrome P450 was not involved. Purified cytochrome P450 reductase could carry out the reduction of SR4233. Rates of reduction of SR4233 in microsomal preparations from the cell lines and in rat liver nuclei correlated with activities of cytochrome P450 reductase. Activation of SR 4233 to cause cellular DNA damage was measured using unscheduled DNA synthesis as an index. Under anaerobic conditions, SR 4233 caused a dose-dependent increase in unscheduled DNA synthesis. Only a slight increase occurred following aerobic incubation. No increase was seen using the reduced metabolites SR 4317 or SR 4330. Of the cell lines studied, Walker cells showed the highest induction of unscheduled DNA synthesis. It was concluded that rates of reduction of SR 4233 did not necessarily reflect the potential DNA-damaging effects of this compound.
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Acid alpha naphthyl acetate esterase (ANAE) and combined ANAE-chloroacetate esterase cytochemistry was performed on 121 bone marrow aspirates from primary myelodysplastic syndromes (MDS) and a secondary dysplasia-megaloblastic anaemia (MA). The investigation demonstrated the presence of abnormal ANAE positive granulocyte populations in a significant proportion of cases. These cells, in which the staining patterns were characterized by atypical granular ANAE positivity and double ANAE-chloroacetate reactions, were shown immunologically to lack the receptor and antigenic characteristics of monocytes and morphologically to be granulocytes. Isoelectric focusing, however, indicated that the atypical esterase cytochemistry of these granulocytes was due to the presence of markedly increased concentrations of ANAE isoenzymes usually found in monocytes. Atypical ANAE-staining granulocytes were particularly evident in MDS marrows showing sideroblastic erythroid changes, whilst in MA they were mainly seen in cases of intermediate severity. It is suggested that these cells are associated with dysmyelopoietic changes in both malignant and non-malignant conditions.
Asthma is the most common chronic medical condition that school teachers may encounter among their pupils. However management of asthma in schools and the role school teachers adopt in this condition has only recently been explored. The aim of this study was to determine teachers' knowledge of asthma and its management. A postal questionnaire was circulated to 199 school teachers from 46 schools in Dublin City. A 74 per cent response rate was obtained. The number of children with asthma as identified by teachers was 7.8 per cent which suggests that asthma may be unrecognised in a number of pupils. Knowledge on signs and symptoms of asthma, provoking factors of asthma and the nature of the disease was generally satisfactory. However, knowledge on asthma medications, the purpose of inhalers and teachers' understanding of the treatment and management of asthma was considered poor. Knowledge on exercise-induced asthma was limited. There is a need to provide school teachers with education on asthma and its management. School policies on asthma also need to be developed with particular reference to action necessary in the event of an acute severe attack of asthma.