Mutational potentiality of stannous chloride: an important reducing agent in the Tc-99m-radiopharmaceuticals.
Stannous chloride (SnCl2) is frequently used in nuclear medicine as a reducing agent to label many radiopharmaceutical products with technetium-99m (99mTc). The aim of the present paper was to study the role of DNA repair genes in the repair of SnCl2-induced damage, using mutant strains of Escherichia coli lacking one or more DNA repair genes. Our results suggest that the product of the xthA gene, exonuclease III, is required for the repair of lesions induced by SnCl2. We further investigated the mutagenic properties of SnCl2 to a molecular level by using the supF tRNA gene as target in a forward mutational system. We have found that the survival of E. coli cells was strongly reduced with increasing concentrations of SnCl2. Moreover, when the shuttle vector pAC189 carrying the supF gene was treated with SnCl2, and then transfected to E. coli, we observed that its transformation efficiency dropped when compared to the non-treated control, with a parallel increase in mutation frequency after the damaged plasmids have replicated in bacterial cells. The mutation spectrum induced by SnCl2 reveals a high frequency of base substitutions, involving guanines. Sequence analysis of 41 independent supF mutant plasmids revealed that 39 mutants contained base substitutions, with 21 G:C to T:A and 17 G:C to C:G transversions. G to T transversions presumably resulted from 8-oxoG. However, the G to C one may be due to a yet unidentified lesion.
Cabral
R E
RE
Laboratório de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. cabral@ibccf.biof.ufrj.br
Leitão
A C
AC
Lage
C
C
Caldeira-de-Araújo
A
A
Bernardo-Filho
M
M
Dantas
F J
FJ
Cabral-Neto
J B
JB
D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000502:physiology; D009154:Mutation; D015609:Organotechnetium Compounds / Q000138:chemical synthesis; D017971:Tin Compounds / Q000009:adverse effects*
D015609:Organotechnetium Compounds; D017971:Tin Compounds; C023599:stannous chloride; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III