Postmeiotic cell stages of repair-proficient ring-X (RX) males were treated with
methyl methanesulfonate (MMS),
ethyl methanesulfonate (EMS),
diethylnitrosamine (DEN) or
ethylnitrosourea (ENU) and then mated to either repair-defective (mei-9L1) or to repair-competent females (mei-9+). Absence of the mei-9+ function resulted in a hypermutability effect to all
alkylating agents (AAs) when they were assayed for their ability to induce
chromosomal aberrations (chromosome loss; CL), irrespective of marked differences in distribution of
DNA adducts brought about by these AAs. This picture is different from that described previously for the induction of point mutations (Vogel et al., 1985a). There, evidence was presented indicating that reduction in
DNA excision repair does not affect point mutation induction (recessive lethals) by those AAs most efficient in ring-
oxygen alkylation such as ENU, DEN, N-
ethyl-N'-nitro-N-nitrosoguanidine (
ENNG), and
isopropyl methanesulfonate (iPMS): the order of hypermutability of AAs with mei-9L relative to mei-9+ was MMS greater than MNU greater than DMN = EMS greater than iPMS = ENU = DEN =
ENNG. When the percentage of lethal mutations induced in mei-9L1 females were plotted against those determined for mei-9+ females, straight lines of following slopes were obtained: MMS = 7.6, MNU = 5.4, DMN = 2.4, EMS = 2.4, and iPMS = ENU = DEN =
ENNG = 1. Those findings, together with the recent observation that AAs do not split into two groups when assayed for their ability to cause CL, point to the involvement of different
DNA alkylation products in ENU- and DEN-induced chromosome loss vs. that of point mutations. It is concluded that with ENU and DEN chromosomal loss results from N-alkylation products whereas point mutations (SLRL) are the consequence of interactions with
oxygen-sites in
DNA. Thus, as a consequence of a very dominating role of O-ethylguanine (and possibly O4-alkylation of
thymine), N-alkylation in
DNA does not contribute measurably to mutation induction in the case of ENU-type
mutagens while O-alkylation, very clearly, does not show a positive correlation with the formation of
chromosome breakage events in Drosophila. Conversely, it appeared that with MMS-type
mutagens (MMS;
dimethyl sulfate, DMS;
trimethyl phosphate,
TMP), alkylation products such as
7-methylguanine and
3-methyladenine, if unrepaired or misrepaired, are potentially mutagenic lesions causing both mutations and
chromosomal aberrations.