Poly-ADP-Ribosylation in the Recovery of Mammalian Cells from DNA Damage

  • Felix R. Althaus
  • Christoph Richter
Part of the Molecular Biology Biochemistry and Biophysics book series (MOLECULAR, volume 37)


It has been known for more than 50 years that glycolysis is inhibited in tissues and cells exposed to alkylating agents (Jany and Sellei 1935; Berenblum et al. 1936; and others). Since 1955, numerous reports have demonstrated that alkylating agents and ionizing radiation lower intracellular NAD levels and this was identified as the underlying metabolic mechanism for the inhibition of glycolysis by these same agents (Holzer et al. 1955, 1958; Roitt 1956; Holzer and Kroeger 1958; Maas et al. 1958; Myers 1960; Kroeger et al. 1960; Hilz et al. 1961, 1963; Kroeger 1963; Myers et al. 1962; Green and Bodansky 1962; Scaife 1963; Whit-field et al. 1964; Altenbrunn et al. 1965; Rüter et al. 1966; Grunicke et al. 1966; Campagnari et al. 1966; Schein et al. 1967; Schein 1969; Yamada et al. 1969; Chang 1972; Harrap and Furness 1973; Whish et al. 1975; Goodwin et al. 1978; Skidmore et al. 1979; Juarez-Salinas et al. 1979; Benjamin and Gill 1980; Jacob-son et al. 1980; Rankin et al. 1980; Busbee et al. 1980; Durkacz et al. 1980; McCurry and Jacobson 1981 b; James and Lehmann 1982; Wielckens et al. 1982; Berger et al. 1983; Ben-Hur et al. 1984, 1985 b; Jonsson et al. 1984; Berger et al. 1986; Sweigert et al. 1986). Cytotoxic agents with no genotoxic activity did not reduce intracellular NAD levels (Davies et al. 1977). In 1975, an important correlation between NAD metabolism and poly(ADP-ribose) biosynthesis was established independently by Whish et al. (1975) and Smulson et al. (1975). Both groups found that the lowering of NAD was accompanied by enhanced utilization of NAD as a substrate for poly(ADP-ribose) biosynthesis. These and numerous subsequent reports have confirmed the importance of ADP-ribosylation reactions as a major pathway of NAD catabolism in tissues and cells subjected to al-kylation or ionizing radiation damage. The possibility that the NAD lowering effect of these treatments could result from concomitant inhibition of NAD biosynthesis or stimulation of microsomal NAD glycohydrolase activity has been excluded (e.g., Juarez-Salinas et al. 1979; Jacobson et al. 1980; Skidmore et al. 1979). Two generalizations of these initial observations have emerged since: (1) the fact that most DNA-damaging agents reduce intracellular NAD levels by this mechanism, and (2) the concept that this mechanism may be responsible for the known cytotoxic effects of genotoxic agents, particularly alkylating agents (vide infra).


L1210 Cell Sister Chromatid Exchange Repair Patch Polymerase Inhibitor Repair Synthesis 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Felix R. Althaus
    • 1
  • Christoph Richter
    • 2
  1. 1.Institut für Pharmakologie und BiochemieUniversität ZürichZürichGermany
  2. 2.Laboratorium für BiochemieETH-ZentrumZürichGermany

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