Pattern of glycogen and iron accumulation in early appearing BHC induced liver lesions and liver tumours.
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Biomedical subjects
Publications and source records attributed to A B Karnik.
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Inbred Swiss mice were fed hexachlorocyclohexane (BHC) at 500 ppm dose level in diet for 2, 4, 6 and 8 months. Later BHC was discontinued for 4 months and subsequently the animals were refed BHC for 1 month. Glucose-6-phosphatase (G6Pase) and fructose-1,6-diphosphatase (FDPase) activity was studied at different time intervals accompanied with changes in glycogen distribution and endoplasmic reticulum (ER) proliferation in hepatocytes. G6Pase and FDPase showed a decline in activities on BHC feeding. The activities of these enzymes showed recovery on BHC discontinuation. The changes were progressive with duration of exposure. After 6 months exposure the biochemical changes became more resistant to recovery. Maximal changes occurred in 8 month-exposure and the changes were irreversible. Glycogen accumulation and depletion followed a definite pattern. After two months of BHC feeding, increase in parenchymal glycogen storage zones was observed. In the later stage of hepatocarcinogenesis and specially in tumors, glycogen was depleted considerably. Smooth endoplasmic reticulum (SER) proliferation was recorded around the 3rd and 4th month. The correlation between glycogen accumulation, SER proliferation, G6Pase and FDPase activity is discussed.
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Inbred Swiss mice were treated with technical BHC (1) orally with the diet or by intubation and (2) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Symptoms of intoxication in the form of convulsions and tendency of circling in one direction with drooping ears were observed alongwith corneal opacity 40 weeks after the experiment. Oral BHC treatment resulted in a significant increase in the incidence of liver tumours and tumours of lymphoreticular tissue. Males and females were equally susceptible. Skin painting of mice did not significantly increase the incidence of tumour.
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Inbred Swiss mice were treated with technical DDT (1) orally with the diet or by intubation; (2) subcutaneously and (3) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Toxic manifestations of DDT were observed in treated mice in the form of tremor, convulsions and corneal opacity usually after 40 weeks. Oral and subcutaneous DDT treatment resulted in a significant increase in the incidence of tumours mainly of lymphoid tissues, lung and liver. The highest tumour incidence was recorded in the group of mice receiving DDT by subcutaneous injections. Males and females were equally susceptible. No evidence of carcinogenicity was observed in the painted group.
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In an attempt to correlate body burden and related liver histopathology after exposure to 500 ppm benzene hexachloride, 6- to 8-wk-old male and female mice were fed benzene hexachloride with their mash diet for a 6-month period. The mice were divided into 8 groups (12/group; 6 experimental, 6 control) and were sacrificed by group monthly. During the first month, 3 groups of mice were sacrificed after 10, 20, and 30 days of treatment, respectively. A dose-related increase in liver weight was found in test animals (P less than .01). The histopathology of liver showed clear, oval cells; hypertrophied cells with foci; and neoplastic nodules that were apparent during the final 3- to 6-month period. Few oval and hypertrophied cells were found in control animals. The alpha isomer concentration of benzene hexachloride rose during the first 2 months of treatment, but declined after that time. A transient rise was noted for the beta isomer concentration of benzene hexachloride at the end of the 6-month period. The gamma isomer concentration was elevated during the initial 3 months of treatment, but declined during the subsequent 3 months. The results present definitive changes suggestive of precancerous states.