ABSTRACT
OBJECTIVE To study the cytotoxic characteristics of nitrogen mustard HN-3 in different cell. METHODS Human epidermal keratinocytes-fetal (HEKf), human dermal fibroblasts-adult (HDFa) and human lung fibroblasts (HLF) cell lines were treated with HN-3100, 300 and 450μmol·L-1 for 0.5, 2, 4, 6, 12, 24 and 48 h, respectively. Multi-parameter analysis technology based on cell imaging was used to examine the effects of HN-3 on cell survival, cell cycle arrest, apoptosis, autophagy and oxidative stress, along with parameters concerning nucleus, cytoskeleton (actin and tubulin), lysosome, nuclear membrane permeability (NMP), mitochondrial membrane potential (MMP) and phosphohistone H 2AX (pH2AX). RESULTS HN-3 caused irreversible cellular damage by significantly decreasing the number of HEKf, HDFa and HLF cells in a time-dependent manner (P<0.01). Before the cell number was reduced robustly, the content of reactive oxygen species and pH2AX significantly increased, but the glutathione content decreased after cells were exposed to HN-3 for 0.5 h (P<0.01). In addition, the content of lyso-some was reduced in HEKf cells at 0.5 h, but increased in HDFa and HLF cells at 0.5 and 2 h respec-tively, accompanied by the increase in microtubule-associated protein 1 light chain 3B (LC3B) puncta.With the significant reduction of the cell number in HEKf cell line, the nuclear intensity increased, nuclear area decreased, the intensity and area of F-actin and α-tubulin decreased, MMP decreased (P<0.01) and lysosomal intensity increased. But the effects of HN-3 on HDFa and HLF cell lines were quite different. The nuclear area increased, the intensity and area of F-actin and a-tubulin increased, MMP increased (P<0.01) and the intensity of lysosome increased. In HLF cells, there was an increase in LC3B puncta (P<0.01). In all the three cell lines, NMP and manganese superoxide dismutase content were increased, and cell cycle arrested at G2 phase. HN-3 Induced early apoptosis in HDFa cells but late apoptosis in HEKf cells. CONCLUSION HN-3 causes DNA damage, oxidative stress and lysosome damage at an early stage, whereas at the late stage, the imbalance of MMP, increase in NMP, and G2 phage arrest are the major cytotoxic effects. Moreover, HN-3 specifically induces nuclear condensation, cytoskeleton protein aggregation and apoptosis in HEKf cell. HN-3 Induces nuclear swelling, and loose cytoskeleton in HDFa cells and HLF cells, eventually inducing early apoptosis in HDFa cells and autophagic death in HLF cells.
ABSTRACT
Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver, skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.
ABSTRACT
123 cases of malignant lymphoma with histologic documentation were reviewed from the files of four contributors from the newly organized Philippine Board of Medical Oncology. Twenty-seven cases of HL and 96 cases of NHL were analyzed according to age, sex, geopgraphic distribution, clinical staging , clinical features, response to therapy, survival time in relation to stage and response to therapy, and non-medical factors which directly affect the prognosis. Multiple drug therapy consisting mainly or cyclophosphamide, vincristine and prednisone were utilized; nitrogen mustard, chlorambucil and mitomycin were also used. Prognosis was good, compatible with long term survival, especially in those who had adequate, continuing therapy. (Summary)
ABSTRACT
Objective To study the effect of Gadd genes expression in surveillance of DNA damage. Methods The human liver tumor cells were treated with alkylating agent(nitrogen mustard) and total RNA was extracted, the expression levels of Gadd genes were determined by RT-PCR. Results Treated with 1 ng/?l nitrogen mustard for 3 h, 24 h, 48 h respectively and with 1 ng/?l, 5 ng/?l nitrogen mustard for 24 h respectively, the expression levels of Gadd genes increased at first (P0.05). Conclusion Gadd genes expression can be used as the indexes in the surveillance of DNA damage induced by nitrogen mustard.
ABSTRACT
Nitrogen mustard encapsulated with liposomes was administered to the rabbits with acute experimental serum sickness(AESS). Then the serum levels of anti-BSA antibodies and circulating; immune complex(CIC), CH50, and WBC count were determined. The ACPase activity of spleen macrophages was measured. And the sections of renal tissues, after HE-stained, were studied for the accumulation of CIC and the pathological changes. It was found that liposome-encapsulated nitrogen mustard can increase the macrophage activity and in turn aggravate the renal damages of AESS rabbits.The results suggest that the renal damages of AESS rabbits can immunopatholo-gically be attributed to the increased activity of macrophages.