Splenic lymphocytes of adult Xenopus respond differentially to PMA in vitro by either dying or dividing: Significance for cancer resistance in this species

Wild-type populations of amphibians, unlike mammalians, appear to be resistant to spontaneous and chemically induced neoplasms. Few true cancers have been reported for non-isogeneic members of Xenopus laevis, despite their widespread use in laboratories around the world. Injection of even the most p...

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Published in:Apoptosis (London) 2003, Vol.8 (1), p.81-90
Main Authors: TAYLOR, S. J, JOHNSON, R. O, RUBEN, L. N, CLOTHIER, R. H
Format: Article
Language:English
Subjects:
Ageing, cell death
Animals
Apoptosis
Biological and medical sciences
Cancer
Cell Cycle
Cell physiology
Cells, Cultured
DNA - metabolism
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Lymphocytes
Lymphocytes - cytology
Lymphocytes - drug effects
Microbiology
Mitogens
Molecular and cellular biology
Neoplasms - chemically induced
Neoplasms - metabolism
Neoplasms - prevention & control
Phorbol Esters
Spleen - cytology
Spleen - drug effects
Time Factors
Xenopus laevis
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Summary:Wild-type populations of amphibians, unlike mammalians, appear to be resistant to spontaneous and chemically induced neoplasms. Few true cancers have been reported for non-isogeneic members of Xenopus laevis, despite their widespread use in laboratories around the world. Injection of even the most powerful direct mammalian oncogens e.g. N-methyl N-nitrosourea, that depleted specific populations of T lymphocytes, did not induce cancer. Phorbol diesters, e.g. PMA, are mitogens and apoptogens in both amphibian, and mammalian immunocytes. In mammalian cells, regulation of the cell cycle and of apoptosis are often intimately linked, however, a disjunction in time between early apoptosis and later cell cycling, has been observed with PMA-treated Xenopus splenocytes. Thus, a particular difference between amphibians and mammals may be the requirement to enter the cell cycle before a progression to death by apoptosis. This hypothesis was tested here using dual staining flow cytometry. Xenopus laevis splenocytes were cultured for 8, 24 and 48 hours with phorbol 12-myristate 13-acetate (PMA), previously shown to be mitogenic and apoptotic with mature Xenopus lymphocytes. The cells were stained with FITC-conjugated Annexin V or with FITC-labeled deoxyuridine triphosphates (FITC-dUTP) to assay for the apoptotic markers phosphotidylserine or DNA strand breaks respectively. Phycoerythrin (PE)-conjugated anti-human proliferating cell nuclear antigen (PE-PCNA) was used as a cell cycle marker that is present during the entire cell cycle. Propidium iodide (PI) binds DNA and was used to assay for late stage apoptosis, as well as to assess DNA content. Significantly higher levels of apoptosis develop rapidly in PMA-exposed splenocytes and are maintained at 24 hours, declining by 48 hours. Cells expressing PCNA or incorporating PI in excess of the normal genomic level were found by 48 hours following PMA exposure. The absence of any significant rise in a small (
ISSN:1360-8185
1573-675X
DOI:10.1023/A:1021605204004