Purpose:　To　investigate　the　molecular　aspects　of　the　synergy　between　ionizing　radiation　and　platinum　(Pt)　chemotherapeutic　agents　in　cancer　treatment　with　chemoradiation　therapy　(CRT)　by　measuring　damages　induced　by　low-energy　electrons　(LEE)　to　DNA　bound　to　cisplatin.　LEE　are　produced　abundantly　by　any　type　of　ionizing　radiation　and　cisplatin　represents　a　typical　Pt-chemotherapeutic　agents.　Materials　and　methods:　Our　strategy　involves　two　parallel　administrations　of　cisplatin　and　irradiation　with　a　4.6　and　9.6　eV　electron　fluence　of　1.1　×　1012:　(1)　LEE　bombardment　of　supercoiled　DNA　and　its　subsequent　reaction　with　cisplatin;　(2)　the　reaction　of　DNA　with　cisplatin　followed　by　LEE　irradiation.　The　damage　yields　for　the　loss　of　supercoiled　(LS),　single-strand　breaks　(SSB)　and　double-strand　breaks　(DSB)　were　obtained　from　gel　electrophoresis　analysis.　Base　modifications　were　revealed　by　treating　the　samples　with　Escherichia　coli　base　excision　repair　endonuclease　(Nth　and　Fpg).　Results:　The　yields　were　deduced　from　the　respective　time–response　for　the　reaction　of　DNA　with　cisplatin.　The　results　show　that　binding　cisplatin　to　DNA　followed　by　LEE　irradiation,　consistently　yields　more　DNA　damages　than　the　reverse　order.　In　comparison　to　non-treated　DNA,　administration　(2)　results　in　an　increase　of　LS　and　SSB　of　1.4–3.3　folds　and　of　DSB　by　more　than　an　order　of　magnitude.　Furthermore,　after　enzyme　treatment,　the　yields　of　DSB　rise　by　factors　of　5.3–15.4,　indicating　a　large　increase　of　clustered　damages,　which　should　at　least　partially　translate　into　an　increase　of　lethal　damages　in　cancer　cells　during　the　CRT.　Conclusions:　Our　results　demonstrate　that　a　strong　synergy　between　radiation　and　cisplatin　can　only　be　achieved　at　the　molecular　level,　if　the　drug　is　present　at　the　time　of　irradiation.　Furthermore,　this　work　confirms　the　LEE　mechanism　previously　proposed　to　explain　the　synergy　between　radiation　and　Pt　drugs　in　CRT.　It　involves　chemical　sensitization　of　DNA　prior　to　irradiation,　to　facilitate　strand　breaks　and　clustered　damages　induced　by　the　highly　reactive　LEE.　©　2017　Informa　UK　Limited,　trading　as　Taylor　&　Francis　Group.