Lethal and mutagenic effects of 5-iodouracil on bacteriophage T4td8rII.

Evidence was obtained which indicates that the lethal effect of 5-iodouracil (IUra) on bacteriophage T4 is not due to a mutagenic process. T4td8rII (thymine requiring, rapid lysis) double mutants were constructed. Reversion of T4td8rII to r(+) was measured. First, reversion by growth in the presence of the structural analogues chlorouracil (ClUra) and bromouracil (BrUra) did not correlate with their relative lethal effects (for mutagenesis: IUra </= ClUra </= BrUra; for lethality: ClUra < BrUra < IUra). Second, reversion frequencies of T4td8rII in infected cells increased linearly with time of growth in the presence of IUra, whereas the frequency of lethality was constant with time. Third, reversion frequencies increased markedly at low levels of IUra substitution, whereas lethal effects were apparent only with extensive IUra substitution. Fourth, the reversion frequency of the nonviable fraction of IUra-substituted T4td8rII (as examined by multiplicity reactivation) did not differ significantly from that of the viable IUra-substituted T4td8 fraction. If mutagenesis caused lethality, then the nonviable T4td8rII fraction should accumulate mutations and have a higher reversion frequency.