 a variety of alkylating mutagens and carcinogens produce pyrimidine adducts in dna that block dna synthesis in vitro . since dna synthesis past the lesion is a necessary step to produce mutations , we investigated the role of the mutagenic metal ion mn++ in facilitating dna synthesis past alkylpyrimidines . in the presence of the natural metal activator 
 mg++ , n3-ethyldeoxythymidine ( n3-et - dt ) and o2-ethyldeoxythymidine ( o2-et - dt ) , present at a single site in dna , blocked in vitro dna synthesis 3 ' to the lesion and after incorporating da opposite each lesion . 
 the presence of mn++ permitted postlesion synthesis with dt misincorporated opposite n3-et - dt and o2-et - dt , implicating these lesions in a.t-->t.a transversion mutagenesis . 
 the dna synthesis block by o4-ethyldeoxythymidine ( o4-et - dt ) in the presence of mg++ was partial and was also removed by mn++ . 
 consistent with in vivo studies , dg was incorporated opposite o4-et - dt during postlesion synthesis , leading to a.t-->g.c transition mutagenesis . 
 we also have discovered a new class of dna adducts , n3-hydroxyalkyldeoxyuridine ( 3-ha - du ) lesions , which are produced by mutagenic and carcinogenic aliphatic epoxides . 
 3-ha - du is formed after initial alkylation at the n3 position of dc followed by a rapid hydrolytic deamination . 
 as observed with the analogous mutagenic n3-et - dt , the ethylene oxide - induced 3-hydroxyethyldeoxyuridine ( 3-he - du ) blocked in vitro dna synthesis , which could be by - passed in the presence of mn++ . 
 the nucleotide incorporated opposite 3-he - du during postlesion synthesis is being identified . 
 these studies suggest a role for mn++ in mediating mutagenic and carcinogenic effects of environmentally important ethylating agents and aliphatic epoxides.imagesfigure 2.figure 4.figure 5.figure 6 . 
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