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Many aneugenic compounds are known to affect one or more components of the mitotic apparatus leading to an erroneous migration of chromosomes. Malsegregation occurs when a chromosome (or a chromatid) fails to migrate and remains at the metaphase plate. Nondisjunction implies the lack of dissociation between sister chromatids and the migration of both together to the same pole. The aim of the present study was to provide evidence that the aneugenic effect of some metal salts is the consequence of malsegregation at anaphase and that it is not caused by nondisjunction mechanisms. The frequencies of lagging chromosomes at anaphase-telophase of mitosis, hypoploid metaphases, and kinetochore-positive micronuclei induced by cadmium chloride, potassium dichromate, and cacodilic acid (dimethylarsinic acid) in MRC-5 human cells were compared. The data indicate that all the tested compounds are able to induce aneuploidy in MRC-5 human cells. Positive, statistically significant correlations were found when kinetochore-positive micronuclei, hypoploidy, and lagging chromosome frequencies were compared. The results suggest that malsegregation is the main mechanism involved in the induction of aneuploidy by metal salts in MRC-5 cells.

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PurposeReactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)–related response to radiotherapy injury in breast cancer patients undergoing RT.Materials and MethodsEighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction–based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects.ResultsSixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment.ConclusionThe analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.