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To determine how radiation-induced arrest in G2 affects the response of mammalian cells to a challenging dose of radiation or to antitumour drugs producing DNA double-strand breaks.V79 fibroblast survival to 5 Gy gamma-rays followed at intervals by 3 Gy irradiation or by contact with an equitoxic dose of neocarzinostatin or etoposide, was measured by clonogenic assays. The pattern of radiation-induced DNA double-strand breaks was determined by filter elution and CFGE (continuous field gel electrophoresis) or PFGE (pulsed-field gel electrophoresis) in G2-arrested cells as well as in nonpre-irradiated asynchronous or synchronized cells. The cell-cycle phase specificity of drug susceptibility was determined in synchronized HeLa cells.Cell kill by radiation-drug combined treatment varied markedly with the time elapsed after priming irradiation. Pre-irradiated, G2-arrested V79 fibroblasts demonstrated excess double-stranded DNA cleavage upon re-irradiation and hypersensitivity to drugs and radiation, although maximum resistance to both neocarzinostatin and etoposide in synchronized HeLa cells was in G2. This effect occurred in the megabase range only, with a peak around 4 Mbp; no change in the electrophoretic migration profile of DNA was observed below 1 Mbp. Moreover, the DNA migration profile and the yield of DNA cleavage in G2-arrested cells were close to those expected from S-phase cells.The available data suggest that mechanisms operating within the radiation-induced G2 block promote susceptibility to DNA double-strand break inducers at this stage. It is also proposed that the conformation of DNA in cells accumulated in G2 following irradiation bears resemblance to that for cells in S phase, due either to active repair mechanisms or to inhibition of chromosome disentanglement at the S-G2 transition.

Saccharomyces cerevisiae (wild-type strain 211) in a stationary phase was exposed to 12-MeV electrons over a dose range of 0. to 700 rads. In one set of experiments a first dose was given in air and a second 15 min later in nitrogen. In a second set of experiments, the first dose was in N/sub 2/ and the second in air. Survival curves were established by varying the size of the second dose. The shoulder of anaerobic curve was completely abolished by pre- irradiation with moderate doses in air. It is suggested that these results indicate a complete overlap of type O and N damage in both directions suggesting that both share a damage pathway in the cell, probably, but not necessarily acting on the same target molecule. (UK)

Three not closely linked genes (r1s, r2sand r3s), a mutation in each of which causes UV- and X-ray-sensitivity of the colony forming ability in haploid and homozygous diploid cells have been identified. In one gene, r3s, two mutations have occurred independently. The effect of the mutated genes on long time repair processes as well as the effect on reversion rates from isoleucine-valine dependence to independence has been investigated. A model to explain the mechanisms changed by the mutated genes is discussed.