Radiosensitization of murine normoblasts in vivo by bromodeoxyuridine to the genotoxicity and cytotoxicity of the bone-seeking radiopharmaceutical 153Sm-EDTMP.
Abstract To establish a basis for a possible strategy for bone marrow ablation or therapy, we examined the effect of bromodeoxyuridine (BrdU) incorporation into DNA on the genotoxic and cytotoxic effects of samarium-153 ethylenediaminetetramethylene phosphonate ((153)Sm-EDTMP) in normoblasts in vivo. Cytotoxicity and genotoxicity were established by time-response curves of polychromatic erythrocyte (PCE) and micronucleated polychromatic erythrocyte (MN-PCE) frequencies, respectively, in mouse peripheral blood samples. The group treated with (153)Sm-EDTMP showed a clear induction of MN-PCEs; however, the group treated with BrdU plus (153)Sm-EDTMP paradoxically showed only a slight increase with respect to untreated controls. Treatment with (53)Sm-EDTMP caused a small reduction in PCE frequency, but exposure to BrdU or to BrdU plus (53)Sm-EDTMP reduced the PCE frequency significantly from 32 h to the end of the experiment. The PCE frequencies in the BrdU plus (53)Sm-EDTMP group were significantly lower than in the BrdU control group at the final time and were much lower than the group treated with only (53)Sm-EDTMP, which returned to basal values. The results suggest the radioinduction of a lethal lesion in BrdU-substituted DNA that cannot be repaired easily and does not permit cell division and micronucleus formation.
Morales-Avila
E
E
Istituto Nacionale de Investigaciones Nucleares, México, DF, México.
Ferro-Flores
G
G
Vallarino-Kelly
T
T
Morales-Ramírez
P
P
D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000494:pharmacology*; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004900:Erythroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000633:toxicity*
D003603:Cytotoxins; D009153:Mutagens; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C061972:samarium Sm-153 lexidronam; D004247:DNA; D001973:Bromodeoxyuridine