Journal of Radiation Research

To test the possibility that the Escherichia coli MutY or MutM protein acts as a 2-hydroxyadenine (2-OH-Ade) glycosylase, we treated double-stranded oligodeoxyribonucleotides containing 2-OH-Ade with the E. coli MutY or MutM protein in vitro. We found that a strand with 2-OH-Ade was a very poor substrate of MutY, irrespective of the base in the complementary strand. Moreover, a strand containing adenine or guanine opposite 2-OH-Ade was also rarely cleaved by MutY. The cleavage of oligonucleotides with 2-OH-Ade by MutM was not observed. These results indicate that neither MutY nor MutM plays an important role in the removal of 2-OH-Ade from DNA.

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The redox chemistry of sanazole, an efficient hypoxic cell radiosensitizer, generally referred to as AK-2123, was studied by pulse radiolysis with e_aq^-, CO₂^-·, 2-propanol radicals and ^·CH ₂OH radicals. AK-2123 reacts with e_aq^-, CO₂^-· and 2-propanol radicals at almost diffusion-controlled rates, producing a nitro radical anion (λ_max=290 nm) within a few microseconds. The decay kinetics of the radical anion was independent of the pH. The radical anion reacts with oxygen with a rate constant of 3.4×10 ⁶ dm³mol^-1 s^-1. An electron-transfer reaction was observed from the thymine radical anion to AK-2123. From redox equilibria with methyl viologen, the one-electron reduction potential of AK-2123 in aqueous solution, determined by pulse radiolysis, was estimated to be -0.33±0.02 V vs. NHE. Depletion of intracellular nonprotein thiols did not mitigate the radiosensitizing affect of the hypoxic radiosensitizer, AK-2123.

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BALB/cHeA (BALB/c) mice are sensitive to radiation lymphomagenesis, while STS/A (STS) mice are resistant. We have selected a recombinant mouse, R1, with a STS-derived D16Mit165-D16Mit34 segment in the vicinity of the centromere of chromosome 16 among progeny from a (CcS-7/Dem×BALB/c)F₁×BALB/c backcross. To test the susceptibility to radiation lymphomagenesis, we generated a genetic cross by mating the male and female R1 progeny obtained by 4-6 backcrosses of R1 to BALB/c. The mice were subjected to 4×1.7 Gy of X-irradiation. Of 120 mice analyzed, 94 developed lymphomas (91, of thymic type; 3, of nonthymic type) within 315 days of observation. The analysis indicated a link between the susceptibility to lymphomagenesis and the marker D16Mit34 on chromosome 16. The mice heterozygous for the BALB/c and STS alleles at D16Mit34 were less sensitive to lymphomagenesis than the mice homozygous at this locus. There was no significant difference in latency among the genotypes. Our study showed the existence of a susceptibility locus for radiation lymphomagenesis on chromosome 16 and revealed aspects of the genetics of lymphoma susceptibility.

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