SYNERGISTIC ACTION OF NITROGEN MUSTARD AND RADIATION IN MICROORGANISMS

Abstract
A technique is described for obtaining reproducible "dose-effect" curves (analogous to radiobiological survival curves) for the inactivation of microorganisms by the bifunctional alkylating agent, nitrogen mustard. The nitrogen mustard dose-effect curves for haploid and diploid yeast are similar in shape to the corresponding X ray survival curves for these organisms, i.e., exponential for haploid and sigmoid for diploid. The LD90 dose ratio between the two ploidies is 4 for HN2 and 5 for X rays. E. coli B/r is more resistant to inactivation by HN2 than is E. coli B. Nitrogen mustard acts synergistically with both X rays and ultraviolet light in the inactivation of E. coli B/r, and diploid yeast, but only with UV in haploid yeast. It is suggested that the formation by HN2 of sub-lethal structural defects in DNA serves to enhance the killing effect of both ultraviolet and ionizing radiations, and that synergistic effects arise through the mutual inhibition of reactivation processes which would otherwise serve to repair or bypass some fraction of the molecular damage.