Induction of Micronuclei, Base-pair Substitution Mutation and Excision-repair Deficient by Polluted Water from Asa River in Nigeria

Asa river is a major river designated to supply millions of people of Ilorin, Kwara State, Nigeria potable water for drinking but its managements is of grave concern due to anthropogenic activities. Thus, evaluation of genotoxicity of this river was carried out by subjecting the water samples and fish therein to three bioassays (Micronucleus (MN) assay, Ames test and SOS-chromo test). Physicochemical parameters and heavy metals were analysed at three different stations (Aliara (SI), Unity (SII) and Tuyil (SIII)) of the river. In SII, most of the heavy metals analysed were above the acceptable limits compare to SI and SIII. The peripheral erythrocyte of the fishes (Oreochromis niloticus, Synodontis batensoda, Synodontis eupterus, Clarias gariepinus and Clarias angullaris) at SI and SII stations showed a significant (p<0.05) induction of MN and different nuclear abnormalities (NA). Water samples from the three stations subjected to Ames test (Salmonella typhimurium TA100) and SOS chromotests (Escherichia coli PQ37) at 25%, 50% and 100% concentrations showed statistically significant (p<0.05) induction of DNA damage at all concentrations in the two tester strains, thus indicating base-pair substitution mutation and excision-repairdeficient, respectively, by the water samples. Therefore, drinking of this water and/or consumption of fish from this river should be taken with caution to avoid a carcinogenic risk.

Determinants of base-pair substitution patterns revealed by whole-genome sequencing of DNA mismatch repair defectiveEscherichia coli

ABSTRACTMismatch repair (MMR) is a major contributor to replication fidelity, but its impact varies with sequence context and the nature of the mismatch. Mutation accumulation experiments followed by whole-genome sequencing of MMR-defectiveE. colistrains yielded ≈30,000 base-pair substitutions, revealing mutational patterns across the entire chromosome. The base-pair substitution spectrum was dominated by A:T > G:C transitions, which occurred predominantly at the center base of 5′NAC3′+5′GTN3′ triplets. Surprisingly, growth on minimal medium or at low temperature attenuated these mutations. Mononucleotide runs were also hotspots for base-pair substitutions, and the rate at which these occurred increased with run length. Comparison with ≈2000 base-pair substitutions accumulated in MMR-proficient strains revealed that both kinds of hotspots appeared in the wild-type spectrum and so are likely to be sites of frequent replication errors. In MMR-defective strains transitions were strand biased, occurring twice as often when A and C rather than T and G were on the lagging-strand template. Loss of nucleotide diphosphate kinase increases the cellular concentration of dCTP, which resulted in increased rates of mutations due to misinsertion of C opposite A and T. In anmmr ndkdouble mutant strain, these mutations were more frequent when the template A and T were on the leading strand, suggesting that lagging-strand synthesis was more error-prone or less well corrected by proofreading than was leading strand synthesis.