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| A POSSIBLE SCREENING-TEST FOR INHERITED P53-RELATED DEFECTS BASED ON THE APOPTOTIC RESPONSE OF PERIPHERAL-BLOOD LYMPHOCYTES TO DNA-DAMAGE |
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| Author(s): CAMPLEJOHN RS, PERRY P, HODGSON SV, TURNER G, WILLIAMS A, UPTON C, MACGEOCH C, MOHAMMED S, BARNES DM |
| Source: BRITISH JOURNAL OF CANCER Volume: 72 Issue: 3 Pages: 654-662 Published: SEP 1995 |
| Times Cited: 30 References: 33 |
| Abstract: The cellular response, in terms of cell cycle arrest(s) and apoptosis. to radiation-induced DNA damage was studied. Experiments were performed on both mitogen-stimulated and resting peripheral blood lymphocytes (PBLs) from normal and cancer-prone (C-P) individuals. The C-P individuals comprised three patients carrying germline p53 mutations and three members of two families apparently without such mutations, but with an inherited defect which results in p53 deregulation as shown by high levels of stabilised p53 protein in normal tissues. Interestingly, mitogen-stimulated PBL, from both normal and C-P individuals failed to demonstrate a GI arrest after gamma radiation. However, a clear difference was seen in the apoptotic response to DNA damage, of PBL from normal and C-P individuals; PBLs from C-P individuals with inherited p53-related defects had a reduced apoptotic response (P = 0.0003). There was a wide margin of separation, with no overlap between the two groups, supporting the possibility of using this altered apoptotic response as a screening test. This simple and rapid procedure could be used to identify those individuals in a C-P family who carry germline p53-related defects. The method appears to detect both individuals with p53 mutations and those apparently without mutations but with other p53-related defects. |
| Document Type: Article |
| Language: English |
| Reprint Address: CAMPLEJOHN, RS (reprint author), UNITED MED & DENT SCH, RICHARD DIMBLEBY DEPT CANC RES, LONDON SE1 7EH, ENGLAND |
Addresses:
1. GUYS HOSP, PAEDIAT RES UNIT, LONDON SE1 9RT, ENGLAND
2. ST JAMES UNIV HOSP, ICRF GENET EPIDEMIOL LAB, LEEDS LS9 7TF, W YORKSHIRE ENGLAND
3. ST JAMES UNIV HOSP, DEPT CLIN GENET, LEEDS LS9 7TF, W YORKSHIRE ENGLAND
4. IMPERIAL CANC RES FUND, LINCOLNS INN FIELDS, LONDON WC2A 3PX, ENGLAND
5. IMPERIAL CANC RES FUND, CLARE HALL LABS, S MIMMS EN6 3LD, HERTS ENGLAND
6. GUYS HOSP, IMPERIAL CANC RES FUND, CLIN ONCOL UNIT, LONDON SE1 9RT, ENGLAND |
| Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS |
| Subject Category: Oncology |
| IDS Number: RT006 |
| ISSN: 0007-0920 |
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