The Effect of N-Nitrosodimethylamine on Enzyme Activities and Histology in the Mouse
This thesis studied the effects of acute, sub-chronic and chronic exposures of NDMA on the enzyme activities of five tumour markers namely: glutathione Stransferase (GST), gamma glutamyl transpeptidase (y-GT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R) and uridyl diphosphogluc...
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Format: | Thesis |
Language: | English English |
Published: |
1999
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Subjects: | |
Online Access: | http://psasir.upm.edu.my/id/eprint/9496/1/FSAS_1999_33_A.pdf |
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Summary: | This thesis studied the effects of acute, sub-chronic and chronic exposures of
NDMA on the enzyme activities of five tumour markers namely: glutathione Stransferase
(GST), gamma glutamyl transpeptidase (y-GT), glutathione peroxidase
(GSH-Px), glutathione reductase (GSH-R) and uridyl diphosphoglucuronyl
transferase (UDPGT) in the liver and kidney of male mice were. Forty-eight male
mice ICR strain, Mus musculus (26-3 8g, 8 weeks old) were divided into four
groups. A single batch consisted of 12 mice; one-half of them for enzyme
activities and the other one-half for histological study. Acute group (n= 12) were
injected with a single dose of 0.5 mg/kg b.w. of NDMA. Sub-chronic group
received 0.25 mg/kg b.w. of NDMA with twice i.p. injection over a one month period. Chronic group (n= 12) were injected with 0.05 mg/kg b.w. of NDMA given
four times over a period of four month. The mice were sacrificed by cervical
dislocation after treatment. In the liver, acute, sub-chronic and chronic exposure to
NDMA showed increased enzyme activities (GST, GSH-R, GSH-Px, y-GT and
UDPGT: except y-GT at acute exposure) in comparison with control groups
(P<0.05). In the kidney, however the effect of NDMA exposure was rather
inconsistent. All the enzyme activities increased in the acute exposure. Meanwhile,
in the sub-chronic and chronic exposure some enzyme activities increased (e.g.:
GST, y-GT and UDPGT) and some enzyme activities (e.g.: GSH-R) did not
change significantly. Administration of NDMA to mice by intraperitoneal
inj ection over various periods of times to a total of 0.05- 0.5 mg/kg body weight
caused the development of the tumour in the liver and kidney. Single acute dose
(0.5 mg/kg b.w. of NDMA) produced anaplastic tumour and tubular degeneration
in the kidney. Prolonged exposure (chronic) of mice to NDMA produced a high
incidence of hepatocellular adenoma and also necrosis in the liver. This study
demonstrated that there is a very strong correlation between enzyme activities and
cell damage. Therefore, it can be concluded that some enzyme activities especially
GST, y-GT and UDPGT can be used as tumour markers. |
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