• Applied Microscopy
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• v.22 no.1
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• pp.113-127
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• 1992

The present study was investigated to elucidate the effects of chlorambucil the heart tissue of various-aged rats. The male rats ranging from 3 to 36 months were used. The cytochemical and biochemical changes in myocardium of the rats were studied in the aspect of free radical roles in aging process. With the goals of evaluating the potential roles of free radicals in aging process, evidence was shought for alterations of myocardial lipid peroxide levels in control and chlorambucil treated rats. The result are summarized as follows: 1. Cytochemical studies showed that the activities of $Mg^{++}$-ATPase and succinic dehydrogenase increased with age. However, these enzyme activities were decreased with treatment of chlorambucil, when compared with control group. Interestingly it was observed that chlorambucil treatment increased the activity of acid phosphatase from 6 months upto 18 months, and decreased after 18 months. 2. The lipid peroxide level in myocatdium was increased with age; chlorambucil-treated group was higher than that of control group. 3. Age-dependent increase in activities of monoamine oxidase, xanthine oxidase and catalase was observed. But the increase of catalase activity was higher than that of monoamine oxidase and xanthine oxidase activity in control group. However, in chlorambucil-treated group, age-dependent decrease of these enzyme activities was observed, and catalase activity was more significant particularly with regard to other enzymes. In consequently, the morphological alterationsof myocardium due to chlorambucil treatment was exclusively observed. We demonstrate that this alteration is occured by lipid peroxidation upon chlorambucil treatment.

• Applied Microscopy
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• v.18 no.2
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• pp.21-33
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• 1988

The purpose of this study was to investigate the effect of chlorambucil on the mouse Leydig cell by electron microscopy. Chlorambucil suspended in the 0.5N sodium bicarbonate(pH 8.0) was injected I.P.(intraperitoneal) at a dosage of level 20mg/kg for 1 weeks, 3 weeks and 5 weeks, respectively. The results obtained from this experiment are as follows: 1. One week after the administration of chlorambucil, there was an increase in heterochromatin, swelling and cristae disruption in some mitochondria, mild vacuolation between cells and the occurrence of membrane bound inclusions in some nuclei. 2. After 3 weeks, smooth endoplasmic reticulum dilations, cytoplasmic vacuolation, mitochondrial swelling, inner mitochondrial cristae disruption, membranous whorls, and intranuclear inclusions were observed in the treated cells. 3. After 5 weeks of treatment, most mitochondria were swollen and their membranes were severely disrupted. Further, smooth endoplasmic reticulum dilations and vacuolation of the cytoplasm were apparent in the treated Leydig cells. In addition numerous membranous whorls and intranuclear inclusion bodies were present. The nuclei displayed invaginatons of the nuclear membrane and large clumps of heterochromatin. From these results it is concluded the longer the duration of chlorambucil administration, the greater the degeneration of the nucleus and cytoplasmic organelles.

• Archives of Pharmacal Research
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• v.20 no.6
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• pp.550-554
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• 1997

Chlorambucil is known to alkylate primarily N7 of guanine and N3 of adenine to induce DNA monofunctional adducts and interstrand cross-links (ISC). We have investigated the sequence specificity for DNA ISC induced by chlorambucil using duplex oligomers containing a defined cross-linkable sequences $ 5^{I}-A*TT, 5^{I}-G*TTor5^{I}-G*CC$ under bar which asterisk indicates the potential cross-linking site and underlined base indicates the potential cross-linking site on the opposite strand. An analysis of 20% denaturing polyacrylamide gel electrophoresis showed that chlorambucil was albe to induce DNA ISC in the duplex oligomers containing a sequence $5^I-GCC$. The formation of DNA ISC was not observed in the duplex oligomers containing sequences $5^I-ATT$. or $5^I-GTT$. These results indicate that chlorambucil induces guanine-guanine DNA ISC but not guanine-adenine or adenine-adenine DNA ISC. In addition, we have tested the ability of chlorambucil to induce DNA ISC within $5^I-GNNC$ or $5^I-GNNC$sequences using duplex oligomers containing the sequence$5^I-G^4G^3G^2^C$. The result of DNA strand cleavage assay showed that DNA ISC was formed at the $5^I-GGC$ sequence (an 1,3 cross-link, $G^1-G^3$) but not at $5^I-GGGC$ (an 1,4 cross-link, $G^1-G^4$) or $5^I-GC$ sequence (an 1,2 cross-link, $G^1-G^2$).

• Applied Microscopy
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• v.20 no.2
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• pp.127-159
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• 1990

This study was investigated to elucidate the effect of chlorambucil on the heart in aging rats. Male rat ranging in age from 3 to 36 months were used. Each age groups(3, 6, 12, 18, 24, 36 months) included control and chlorambucil treated rats. As a part of the study, the ultrastructural changes in the left ventricular myocardial cells were described by using the qualitative and morphometric techniques. The results are summarized as follows. Age associated ultrastructural changes included: an increase in vacuoles, protrusion of plasma membranes, lipid droplets, and lipofuscins in myocardium of control groups. These changes which begin to occur at 12 months and continue through 36 months. At the 36 months some instance of unusual formation of contraction band and separation of intercalated discs were encountered. Morever, these changes and contents with chlorambucil treatment were remarkably increased in comparison with control groups. Age-dependent changes of control group measured with morphometry were not observed in the volume densities of mitochondria and myofibrils. But there was increase in interstitium. On the other hand decrease in sarcoplasmic reticulum and T-tubule system. In chlorambucil treated groups, volume densities of mitochondria and interstitium were increased in comparison with those of the control groups. But sarcoplasmic reticulum and T-tubule system were remarkably decreased.

• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.291-301
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• 2005

Objective : Anticancerous and host safety effects of the combination of Astragali Radix and chlorambucil are studied when it is applied to leukemia cell(P388D1 cell) related disease. Methods : After 5 groups of mice are treated by respective procedures (HG, CHL, HG+CHL, etc), the quantitative analyses (cell proliferation assay, mutagenesis test, survival rate, weight shift observation, tissue and blood analyses, etc) are conducted. Results : While sole injection of Astragali Radix extends the survival period and deter the liver and marrow function deterioration, combined injection (HG+CHL) shows more strong anticancerous effect than sole injection of Astragali Radix or Cholrambucil, and also does not cause any mutation on the normal cells and virulence on marrow and liver caused by leukemia. Conclusions : The combined application of Astragali Radix and chlorambucil has more effective anticancerous and host safety effects than independent use of them.

• Journal of Veterinary Clinics
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• v.34 no.3
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• pp.193-196
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• 2017

A 14-year-old, castrated male, domestic shorthair cat was referred for gastrointestinal (GI) signs, including nausea, regurgitation, anorexia, and weight loss. Abdominal ultrasonography revealed thickening of the wall of the gastric and proximal duodenum, moderately enlarged mesenteric lymph nodes, and coarse echotexture of the splenic parenchyma. The results of the feline leukemia virus test were positive. Based on gastrointestinal endoscopic characteristics and histopathological examinations, low-grade alimentary lymphoma was identified in multiple regions of the gastrointestinal tract. The patient was treated with oral prednisolone and chlorambucil chemotherapy, and the clinical signs resolved gradually. During serial follow-up, ultrasonographic findings demonstrated decreases in the duodenal wall thickness and size of the abdominal lymph nodes over a period of 550 days. Survival time was 886 days with prednisolone and chlorambucil chemotherapy. This report describes clinical features, imaging findings, endoscopic characteristics, histopathological features, and long-term management with chlorambucil chemotherapy in a case of feline low-grade alimentary lymphoma.

• Korean Journal of Veterinary Research
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• v.63 no.4
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• pp.38.1-38.6
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• 2023

Canine T-zone lymphoma (TZL) is an indolent form of T-cell lymphoma. Conservative management is usually recommended; however, chemotherapy may be considered for symptomatic or progressive cases. Herein, we describe two dogs with generalized peripheral lymphadenopathy and peripheral blood lymphocytosis at presentation. One dog presented with gross lesions on the tongue. Flow cytometric immunophenotyping and cytological examinations demonstrated findings consistent with those of TZL. Chemotherapy with chlorambucil and prednisolone was administered, which resulted in improvement of the condition without any adverse events. Chemotherapy with chlorambucil may be considered as an appropriate choice for treating canine TZL.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.109-110
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• 2003

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.109-110
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• 2003

To validate a novel mouse model, gpt delta, for in vivo mutagenesis, the Mammalian Mutagenesis Society (MMS), a subgroup of the Environmental Mutagen Society of Japan (JEMS) (JEMS/MMS), performed a collaborative study as the third trial for transgenic animal assay. In this mouse model, point mutations and deletions re separately identified by gpt (6-thioguanine-resistant) and Spi- (sensitive to P2 interference) selections, respectively.(omitted)

• Journal of Veterinary Clinics
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• v.19 no.4
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• pp.429-432
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• 2002

Chronic Iymphocytic leukemia is a general disease that evolves over a longer duration and is characterized by more mature and well-differentiated Iymphocytes in blood and bone marrow than those seen in acute leukemia. This report presents a 2-year-old mix neutered male dog with seizure, ascites, and transmissible venereal tumor. Diagnostic works-up concluded chronic Iymphocytic leukemia. Chemotherapy composed of chlorambucil and prednisolone has been applied to the patient until now. Remission of almost manifestations was achieved, and the quality of life improved.