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The gross and cellular response of a rat mammary tumour to single doses of cyclophosphamide
Affiliation:1. Vaccine and Infectious Diseases Laboratory, Department of Immunology and Pathology, Monash University, Melbourne, Australia;2. Womens Cancer Research Centre, Royal Women’s Hospital, Melbourne, Australia;1. State Key Labobatory of Hulless and Yak Germplasm Resources and Genetic Improvement, Lhasa, Tibet, 850000, China;2. Colleges of Life Science and Technology, Dalian University, Dalian Economic-Technological Development Zone, Liaoning, 116622, China;3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China;4. Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China;5. Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, China;1. Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), No. 2900, Hosur Road, Bangalore, 560029, India;2. Department of Clinical Psychopharmacology and Neurotoxicology, NIMHANS, No. 2900, Hosur Road, Bangalore, 560029, India;3. Institute of Bioinformatics, International Technology Park, White Field, Bangalore, 560066, India;4. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690525, India;5. Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India;6. Department of Biostatistics, NIMHANS, No. 2900, Hosur Road, Bangalore, 560029, India
Abstract:The response of a transplanted mammary carcinoma of Wistar rats, to single intraperitoneal doses of cyclophosphamide (25–250 mg kg−1) has been assayed by measurement of; delay in growth of the tumour between 9 and 25 mm; cell survival in vitro, 3 and 24 hr after in situ treatment; tritiated thymidine autoradiography and Feulgen microdensitometry of histological material. All three methods of assay indicate that at 9 mm diameter the tumour contains a subpopulation of malignant cells relatively resistant to cyclophosphamide doses in excess of 50 mg kg−1. The in vitro cell survival assay suggests that these cells comprise 40–50% of the clonogenic population and are capable of considerable in situ repair of potentially lethal damage within 24 hr of treatment. Cellular repopulation from this resistant component, after 150 mg kg−1 of drug, is delayed for 6 or more days and restoration to near pre-treatment status only achieved by 10 days, in this rapidly-growing tumour.
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