1 Apopotosis is a remarkably stereotyped morphological event across all tissues in response to a vast array of dam aging agents.
2 Our very existence depends upon a willing exchange of old life for new: apoptotic cell death is our guardian and saviour from genetic damage.
3 There is a close link between cell proliferation and apoptosis: When a cell picks up the machinery to prolifer ate it also acquires an abort pathway - 'better dead than wrong'.
4 A wide variety of highly conserved genes have been implicated in triggering apoptosis.
5 The release of DNA loops from the nuclear scaffold is a more crucial intracellular event than DNA 'laddering' in apoptotic cells.
6 The manipulation of apoptotic rates in many of the common diseases in man will be a major therapeutic strategy in the future.
Kerr Jfr, Wyllie AH & Currie ARApoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer1972; 68: 239-57.
2.
Ellis HM & Horvitz HRGenetic control of programmed cell death in the nematode C. elegans. Cell1986; 44: 817-29.
3.
Arends MJ, Morris RG & Wyllie AHApoptosis. The role of the endonuclease. American Journal of Pathology1990; 136: 593-608.
4.
Peitsch MC, Mannherz HG & Tschopp J.The apoptosis endonucleases: cleaning up after death? Trends in Cell Biology1994; 4: 37-41.
5.
Oberhammer F. , Wilson JW, Dive C. et al. Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO Journal1993; 12: 3679-84.
6.
Filipski J., Leblanc J., Youdale T., Sikorska M. & Walker PRPeriodicity of DNA folding in higher order chromatin structures. EMBO Journal1990; 9: 1319-27.
7.
Sun XM, Snowden RT, Dinsdale D., Ormerod MG & Cohen GMChanges in nuclear chromatin precede internucleosomal DNA cleavage in the induction of apoptosis by etoposide. Biochemical Pharmacology1994; 47: 187-95.
8.
McCabe MJ & Orrenius S.Genistein induces apoptosis in immature human thymocytes by inhibiting topoisomerase-II . Biochemical Biophysical Research Communications1993; 194: 944-950.
9.
Cohen JJ & Duke RCGlucocorticoid activation of a calcium dependent endonuclease in thymic nuclei leads to cell death. Journal ofImmunology1984; 132: 38-42.
10.
Kurl RN, Abraham M. & Olnes MJEarly effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on rat thymocytes in vitro. Toxicology1993; 77: 103-114.
11.
Duke RC, Chervenak R. & Cohen JJEndogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proceedings of the National Academy of Science USA 1983; 80: 6361-65.
12.
Orrenius S. , McCabe MJ & Nicotera P.Ca(2+)-dependent mechanisms of cytotoxicity and programmed cell death. Toxicology Letters1992; 64-65: 357-64.
13.
McConkey DJ , Hartzell P., Nicotera P. & Orrenius S.Calcium-activated DNA fragmentation kills immature thymocytes. FASEB Journal1989; 3: 1843-9.
14.
McConkey DJ , Hartzell P. & Orrenius S.Rapid turnover of endogenous endonuclease activity in thymocytes: effects of inhibitors of macromolecular synthesis. Archives of Biochemistry andBiophysics1990 ; 278: 284-7.
15.
McConkey DJ , Nicotera P., Hartzell P., Bellomo G., Wyllie AH & Orrenius S.Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Archives of Biochemistry and Biophysics1989; 269: 365-70.
16.
Ray SD, Kamendulis LM, Gurule MW, Yorkin RD & Corcoran GBCa2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. FASEB Journal1993; 7: 453-63.
17.
Fesus L.Biochemical events in naturally occurring forms of cell death. FEBS1993; 328: 1-5.
18.
Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM & Haslett C.Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. Journal of Clinical Investigation1989; 83: 865-75.
19.
Savill JS, Dransfield I., Hogg N. & Haslett C.Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature1990; 343: 170-3.
20.
Duvall E., Wyllie AH & Morris RGMacrophage recognition of cells undergoing programmed cell death (apoptosis) . Immunology1985; 56: 351-8.
21.
Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL & Henson PMExposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. Journal ofImmunology1992; 148: 2207-16.
22.
Vaux D., Cory S. & Adams J.Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature1988; 335: 440-2.
23.
Reed JCBcl-2 and the regulation of programmed cell death. Journal of CellBiology1994; 124: 1-6.
24.
Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL & Korsmeyer SJBcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell1993; 75: 241-51.
25.
Veis DJ, Sorenson CM, Shutter JR & Korsmeyer SJBcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell1993 ; 75: 229-40.
26.
Oltvai ZN, Milliman CL & Korsmeyer SJBcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell1993; 74: 609-19.
27.
Boise LH, Gonzalez-Garcia M., Postema CE, et al. bclx, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell1993; 74: 597-608.
28.
Yin XM, Oltvai ZN & Kormeyer SJBH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerisation with Bax. Nature1994; 369: 321-3.
29.
Hengartner MO, Ellis RE & Horvitz HRCaenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature1992 ; 356: 494-9.
30.
Hengartner MO & Horvitz HRActivation of C. elegans cell death protein CED-9 by an amino acid substitution in a domain conserved in Bcl-2. Nature1994; 369: 318-20.
31.
Manfredini R., Grande A., Tagliafico E. et al. Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation. Journal of Experimental Medicine1993; 178: 381-9.
32.
Wilson KP, Black J-A F, Thomson JA et al. Structure and mechanism of interleukin-1β converting enzyme . Nature1994; 370: 270-5.
33.
Yuan J., Shaham S., Ledoux S., Ellis HM & Horvitz HRThe C. elegans cell death gene, ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme. Cell1993; 75: 641-52.
34.
Miura M., Zhu H., Rotello R., Hartwieg EA & Yuan J.Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell1993; 75: 653-60.
35.
Gagliardini V., Fernandez P-A., Lee Rkk et al. Prevention of vertebrate neuronal death by the crmA gene. Science1994; 263: 826-8.
36.
Evan GI, Wyllie AH, Gilbert CS et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell1992; 69: 119-29.
37.
Anilkumar TV , Sarraf CE, Hunt T. & Alison MRThe nature of cytotoxic drug-induced cell death in murine intestinal crypts. British Journal of Cancer1992; 65: 552-8.
38.
Amati B., Littlewood TD, Evan GI & Land H.The c-myc protein induces cell cycle progression and apoptosis through dimerisation with max. EMBO Journal1987; 12: 5083-7.
39.
Lowe SW, Schmitt EM, Smith SW, Osborne BA & Jacks T.p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature1993; 362: 847-9.
40.
Merritt AJ, Potten CS, Kemp CJ et al. The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Research1994; 54: 614-17.
41.
Caelles C., Helmberg A. & Karin M.p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature1994; 370: 220-3.
42.
Nagata S.Mutations in the Fas antigen in lpr mice. Immunology1994; 6: 3-8.
43.
Yonehara S. , Ishii A. & Yonehara M.A cell killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumour necrosis factor. Journal of Experimental Medicine1989 ; 169: 1747-56.
44.
Trauth BC, Klas C., Peters Amj et al. Monoclonal antibody-mediated tumour regression by induction of apoptosis. Science1989; 245: 301-5.
45.
Suda T., Takahashi T., Goldstein P. & Nagata S.Molecular cloning and expression of the Fas ligand: a novel member of the tumour necrosis family. Cell1993; 75: 1169-78.
46.
Ogasawara J. , Watanabe-Fukunaga R., Adachi M. et al. Lethal effect of the anti-Fas antibody in mice. Nature1993 ; 364: 806-9.
47.
Raff MC, Barres BA, Burne JF, Coles HS, Ishizaki Y. & Jacobson MCProgrammed cell death and the control of cell survival: lessons from the nervous system. Science1993; 262: 695-700.
48.
Williams GTApoptosis in the immune system. Journal of Pathology1994; 173: 1-4.
49.
Liu Y-J., Joshua DE, Williams GT, Smith CA, Gordon J. & MacLennan Icm.Mechanism of antigen-driven selection in germinal centres. Nature1989; 342: 929-31.
50.
Rabizadeh S. , LaCount DJFriesen PD & Bredesen DEExpression of the baculovirus p35 gene inhibits mammalian neural cell death. Journal of Neurochemistry1993; 61: 2318-21.
51.
Debbas M. & White E.Wild-type p53 mediates apoptosis by EIA, which is inhibited by E1B. Genes & Development1993; 7: 546-54.
Gougeon M.-L. & Montagnier L.Apoptosis in AIDS. Science1993; 260: 1269-70.
54.
Alison MR & Sarraf CEApoptosis: a gene-directed programme of cell death. Journal of the Royal College of Physicians1992; 26: 25-35.
55.
Sarraf CE, Ansari TW, Conway P., Notay M., Hill S. & Alison MRBromodeoxyuridine-labelled apoptosis after treatment with antimetabolites in two murine tumours and in small intestinal crypts. British Journal of Cancer1993; 68: 678-80.
56.
Dive C. & Wyllie AHApoptosis and cancer chemotherapy. In: Hickman JA & Tritton TR (eds). Cancer Chemotherapy. Blackwell Scientific Publications : Oxford, 1993; 21-56.
57.
El-Azzouzi B., Tsangaris GT, Pellegrini O., Manuel Y., Benveniste J. & Thomas Y.Cadmium induces apoptosis in a human T-cell line. Toxicology1994; 88: 127-39.
58.
Zwi LJ, Baguley BC, Gavin JB & Wilson WRThe morphological effects of the anti-tumor agents flavone acetic acid and 5,6-dimethyl xanthenone acetic acid on the colon 38 mouse tumor. Pathology1994; 26: 161-9.
59.
Morris SM, McGarrity LJ, Domon OE et al. The role of programmed cell death in the toxicity of the mutagens, ethylmethanesulfonate and N-ethyl-N'nitrosourea, in AHH-1 human lymphoblastoid cells. Mutation Research1994306: 19-34.
60.
Hinoshita F. , Hardin JA & Sherr DHFluoranthine induces programmed cell death and alters growth of immature B cell populations in bone marrow cultures. Toxicology1992; 73: 203-18.
61.
Zucker RM, Elstein KH, Thomas DJ & Rogers JMTributyltin and dexamethasone induce apoptosis in rat thymocytes by mutually antagonistic mechanisms. Toxicology and Applied Pharmacology1994; 127: 163-70.
62.
Blankenship LJ , Manning Fcr, Orrenstein JM & Patierno SRApoptosis is the mode of cell death caused by carcinogenic chromium. Toxicology and Applied Pharmacology1994; 126: 75-83.
63.
Burchiel SW , Davis DA, Ray SD & Barton SLDMBA induces programmed cell death (apoptosis) in the A20.1 murine B cell lymphoma. Fundamental and Applied Toxicology1993; 21: 120-4.
64.
Columbano A. , Ledda-Columbano GM, Coni PP et al. Occurrence of cell death (apoptosis) during the involution of rat liver hyperplasia. Laboratory Investigation1985; 52: 670-3.
65.
Alison MR, Wilkins Mje, Walker SM & Hully JRCell population size control in the rat liver: the response of hepatocytes in various proliferative states to a mitogenic stimulus. Epithelia1987; 1: 53-64.
66.
Bursch W., Taper HS, Lauer B. & Schulte-Hermann R.Quantitative histological and histochemical studies on the occurrence and stages of controlled cell death (apoptosis) during regression of rat liver hyperplasia. Virchows Archives [Cell Pathology]1985; 50: 153-66.
67.
Bursch W., Oberhammer F., Jirtle RL et al. Transforming growth factor-β1 as a signal for induction of cell death by apoptosis. British Journal of Cancer1993; 67: 531-6.
68.
Sarraf CE & Bowen IDThe occurrence of apoptosis in tumours and its effect on neoplastic development . In: Columbano A, Feo F, Pascale R, Pani P (eds). Chemical carcinogenesis 2. Modulating factors. Plenum: New York, 1991; 553-62.
69.
Sarraf CE & Bowen IDKinetic studies on a murine sarcoma and an analysis of apotosis. British Journal of Cancer1986; 54: 989—98.
70.
Arends MJ, McGregor AH & Wyllie AHApoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes. American Journal of Pathology1994; 144: 1045-57.
71.
Columbano A. , Ledda-Columbano GM, Rao PM, Rajalakshmi S. & Sarma Dsr.Occurrence of cell death (apoptosis) in preneoplastic and neoplastic liver cells. American Journal of Pathology1984; 116: 441-6.
72.
Gerbracht U. , Bursch W., Kraus P. et al. Effects of hypolipidaemic drugs nafenopin and clofibrate on phenotypic expression and cell death (apoptosis) in altered foci of rat liver. Carcinogenesis1990; 11: 617-24.
