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| THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS |
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| Author(s): CLARKE AR, PURDIE CA, HARRISON DJ, MORRIS RG, BIRD CC, HOOPER ML, WYLLIE AH |
| Source: NATURE Volume: 362 Issue: 6423 Pages: 849-852 Published: APR 29 1993 |
| Times Cited: 2,213 References: 26 |
| Abstract: DEATH by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy1. Apoptosis can be initiated by various agents1-5 and may be a result of expression of the oncosuppressor gene p53 (refs 6-8). Here we study the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca2+-dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Our results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage. |
| Document Type: Article |
| Language: English |
| Reprint Address: CLARKE, AR (reprint author), UNIV EDINBURGH, SCH MED, DEPT PATHOL, CANC RES CAMPAIGN LABS, TEVIOT PL, EDINBURGH EH8 9AG, MIDLOTHIAN SCOTLAND |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: KZ563 |
| ISSN: 0028-0836 |
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