Participation of BER and NER pathways in the repair of DNA lesions induced at low N-nitrosodiethylamine concentrations.
In the present work, we evaluated (p < 0.05) the participation of base excision repair (BER) and nucleotide excision repair (NER) mechanisms in repairing DNA lesions induced by N-nitrosodiethylamine (NDEA) at 1.5 ng/mL-36.5 microg/mL, through cell survival, in different single and double Escherichia coli DNA repair mutants (uvrA, uvrB, uvrC, fpg, nth, xthA, fpg/nth, uvrA/fpg, fpg/xthA, mutY, and fpg/mutY), using pre-incubation periods of 90 min. Mutant strains BH20 (fpg) and AB1886 (uvrA) showed microsomal enzyme (S9 mix) independent NDEA cytotoxicity. Cytotoxicity was also detected at lowest NDEA concentrations, in the presence of S9 mix, with strains BH980 (mutY) and BH990 (fpg/mutY). NDEA cytotoxicity, without S9 mix, was detected for mutant strains AB1884 (uvrC) and AB1885 (uvrB). Through SOS chromotest with 90 min of pre-incubation for uvrA and nth strains, only NER was shown to be required for repairing NDEA-induced lesions with or without metabolic activation. PQ37 and PQ66 strains, both uvrA mutants, showed different levels of NDEA sensitivity. The findings suggest that, under the used conditions, and at low concentrations, NDEA-induced lesions require both repair pathways.
Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87 fds., 4 Andar, 20551-030 Rio de Janeiro, Brazil.
Claudia Alessandra Fortes
CA
Aiub
José Luiz
JL
Mazzei
Luis Felipe Ribeiro
LF
Pinto
Israel
I
Felzenszwalb
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D015169:Colony Count, Microbial; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D004269:DNA, Bacterial / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013014:SOS Response, Genetics / Q000187:drug effects* / Q000235:genetics
D000477:Alkylating Agents; D004269:DNA, Bacterial; D004052:Diethylnitrosamine