The lethal action of monofunctional and bifunctional alkylating agents on T7 coliphage

Abstract

1. 1. With the T7 coliphage, the lethality caused by a monofunctional alkylating agent (ethyl methanesulfonate) as well as by bifunctional alkylating agents (nitrogen mustard, diepoxybutane, myleran) is a single-hit process. 2. 2. With ethyl methanesulfonate, the efficient hit must be an alkylation, a depurination or a single-strand break within a sensitive target. The target might be the portion of one of the DNA strands containing the information for the early enzymes needed for the phage replication. The lethality increases steadily after the end of the ethyl methanesulfonate treatment; this aggravation is due to depurination and/or the formation of single-strand breaks which are more efficient than alkylations. These features are characteristic of a monofunctional type of action. 3. 3. The causes of lethality consecutive to a treatment with nitrogen mustard are interstrand crosslinks at the beginning, and double-strand scissions afterwards. The level of alkylation is too low for alkylation, depurination or single-strand break to be a significant cause of death. The evolution of lethality after a 0.5-h treatment with nitrogen mustard is complex: it increases first, passes through a maximum, then decreases, reflecting the appearance and disappearance of the interstrand crosslinks; this resurrection is followed by a slow increase of lethality as the double-strand scissions are formed. These features are characteristic of a bifunctional type of action. 4. 4. Myleran presents all the features of a monofunctional type of action. No interstrand DNA crosslink has ever been found after the action of myleran, nor after the action of dimethylmyleran. 5. 5. Lethality after diepoxybutane results from the sum of the two types of action, bifunctional and monofunctional. The lethality does not change during the first few days after the end of the treatment.