Maria Paula Curado

Human micronucleus counts are correlated with age, smoking, and cesium-137 dose in the Goiânia (Brazil) radiological accident

A random sample of 276 people representing control, direct exposure, and probable indirect exposure in the Goiânia, Brazil radiological accident was examined using micronuclei as indicators of cytogenetic damage. The Goiânia subjects were analyzed for interactions of age, lifestyle, and ionizing radiation dose. Increases in micronucleus frequencies were most strongly correlated with the dose of ionizing radiation, but age, alcohol consumption, and smoking habits also affected micronucleus frequencies. Despite these additional influences, micronucleus frequencies can be useful as biological dosimeters.

Monitoring hprt mutant frequency over time in T-lymphocytes of people accidentally exposed to high doses of ionizing radiation

Modern technologies have provided the opportunity to monitor mutations in people in vivo. The subjects of this study were accidentally exposed to 137Cesium in a radiological accident that occurred in September 1987 in Goiânia, Brazil, during which more than 150 people received doses greater than 0.1 Gy and as high as 7 Gy. The objective of this study was to determine how long the hprt mutant T‐cells in the peripheral blood contribute to mutant frequency by examining the time‐course of the T‐lymphocyte response to ionizing radiation. This report describes the results obtained over a period of 2.3 to 4.5 years subsequent to the accident, from 11 subjects with doses ranging from 1 to 7 Gy, and from nine control subjects selected from the same population. The mean ln MF (±SE) of the control group was 2.5 (±0.2) + ln 10−6. The exposed group had a significantly increased mutant frequency; the mean In MF (± SE) were 3.3 (±0.3) + ln 10−6, 2.8 (±0.2) + ln 10−6, and 2.3 (±0.2) + ln 10 −6, in the years 1990–1992 respectively. Based on the decline of mutant frequency and using Bucktons models [Buckton et al. (1967): Nature 214:470–473], we demonstrated that mutant T‐cells have a short‐term memory with a half‐life of 2.1 years. This relatively short half‐life limits the effective use of the hprt assay as the method of choice to monitor past exposure. The data also demonstrate a positive correlation with age, and an inverse correlation with plating efficiency.

Microsatellite mutations in the offspring of irradiated parents 19 years after the Cesium-137 accident

In September of 1987, a radiotherapy unit containing 50.9 TBq of Cs(137)Cl was removed from an abandoned radiotherapy clinic. This unit was subsequently disassembled leading to the most serious radiological accident yet to occur in the Western hemisphere. This event provides an opportunity to assess the genetic effects of ionizing radiation. We surveyed genetic variation of 12 microsatellite loci in 10 families of exposed individuals and their offspring and also in non-exposed families from the same area of Goias state. We found an increase in the number of new alleles in the offspring of the exposed individuals. The mutation rate was found to be higher in the exposed families compared to the control group. These results indicated that exposure to ionizing radiation can be detected in offspring of exposed individuals and also suggest that the elevated microsatellite mutation rate can be attributed to radioactive exposure.

Involvement of CYP1A1, GST, 72TP53 polymorphisms in the pathogenesis of thyroid nodules

Specific genotypes appear to be related to the development of thyroid disease. We examined whether polymorphisms of the genes CYP1A1, GSTM1, GSTT1, and TP53 at codon 72 are associated with increased risk for thyroid nodules. Blood samples were obtained from 122 thyroid patients with nodules and from 134 healthy control individuals from Goiânia city, GO, Brazil. We found no significant association of CYP1A1m1 and CYP1A1m2 genotypes with thyroid diseases (P > 0.05). The null genotypes of GSTM1 and GSTT1 genes were predominant in patients with nodules, indicating that individuals that possess these genotypes have a predisposition for thyroid disease. The genotype p53Arg Arg was associated with a low risk for thyroid cancer (OR = 0.15; P < 0.0001), indicating that the arginine allele in homozygosis could have a protective effect against carcinogenesis. On the other hand, the p53ArgPro genotype was significantly associated with malignant neoplastic nodules (OR = 3.65; P = 0.001). Interindividual variation in susceptibility to thyroid diseases could provide new perspectives for early diagnosis, prognosis and treatment, indicating which patients with thyroid nodules will benefit from treatment, depending on specific polymorphic profiles.

Molecular analysis of T‐lymphocyte HPRT‐ mutations in individuals exposed to ionizing radiation in Goiânia, Brazil

We have characterized 54 HPRT‐ point mutations in T‐lymphocytes from 17 individuals exposed to ionizing radiation of 137Cs in Goiânia, Brazil and compared this spectrum to that of 30 HPRT‐ mutants from 9 unexposed Brazilian controls. The average internal exposure of the exposed group was 205 mCi, and the average external exposure was 1.7 Gy. The average HPRT‐ mutant frequency for the exposed group was 13.3 × 10‐5, approximately a 10‐fold increase over the mutant frequency of the unexposed controls, which was 1.56 × 10‐5. The types of point mutations characterized included base substitutions, small deletions, frameshifts, in‐sertions, complex mutations, and losses of exon sequences from the mRNA. The relative frequency of the different mutation types was similar in the two studied groups. However, in our study the distribution of events within the hprt coding sequence seemed to cluster at the same regions of the gene. These observations imply that the hprt gene does not present a homogeneous target to radiation mutagenesis, and perhaps this class of information may be used to detect radiation exposure in human populations. Environ. Mol. Mutagen. 29:107‐116, 1997.

WITHDRAWN: Human papillomavirus detection and genotyping in squamous cell carcinomas of the larynx

Antonio Márcio Teodoro Cordeiro Silva a,b, Cesar Augusto Sam Tiago Vilanova-Costa a,b, Sheila Freires de Oliveira a, Cláudio Carlos da Silva a,c, Maria Paula Curado b, Aparecido Divino da Cruz a,b,c a Replicon Research Nucleus, Catholic University of Goias, Goiania, Brazil b Goiania’s Population-Based Cancer Registry, Association of Cancer Combat of Goias, Goiania, Goias, Brazil c Laboratory of Molecular Genetics and Human Cytogenetics – LaGene, Secretary of Health, Goiania, Goias, Brazil

CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study.

We investigated the association between an aggrecan gene (ACAN) polymorphism and lumbar disc herniation (LDH). This was a case-control study with quinquennial age and gender groups. The study comprised 119 men and women aged between 20 and 60 from Goiânia (Brazil). Of these, 39 were allocated to the case group (Ca) and 80 to the control group (Ct). We gathered sociodemographic and clinical data, and peripheral blood samples. DNA was isolated for genotyping the ACAN variable number tandem repeat (VNTR) via conventional polymerase chain reaction (PCR). Data were statistically analyzed using the chi-square test, multiple comparison analysis, the Student t-test, and odds ratios, with a level of significance set at 5% (P ≤ 0.05). The groups were homogenous in terms of sociodemographic, anthropometric, and life style variables. The allele score for the ACAN VNTR was significantly lower in volunteers with LDH; the A22 allele was significantly more prevalent in this same group; the Ca group presented greater frequency of short alleles A13-A25, whereas the Ct group presented a higher frequency of long alleles. However, this difference was not statistically significant. In both groups, the most common alleles were A28, A27, and A29, and the A26/A26 genotype was significantly more common in the Ca group. The results showed an association between short alleles and LDH among the investigated adults (Ca), corroborating the hypothesis that aggrecan with shorter repeat lengths can lead to a reduction in the physiological proteoglycan function of intervertebral disc hydration and, consequently, increased individual susceptibility to LDH.

Polimorfismo de TP53 nos Carcinomas Tiroideanos: estudo molecular e meta-análise

Resumo: nossa proposta foi avaliar o polimorfismo do gene TP5372 e a associacao deste com o risco de desenvolvimento do câncer da tireoide. Para avaliar o papel de tal polimorfismo, 35 casos de câncer de tireoide foram comparados ao grupo controle de 134 individuos saudaveis. A determinacao do polimorfismo do gene TP5372 foi feita por PCR e incluido na meta-analise de estudos caso-controle com pacientes com carcinomas tiroideanos utilizando o metodo de DerSimonian-Laird. A frequencia do alelo p53Arg foi significativamente maior em ambos os grupos analisados. A comparacao da frequencia genotipica dos pacientes com o grupo controle demonstrou que genotipo p53Arg Arg apresenta menor risco para desenvolvimento de câncer, sugerindo que a presenca do alelo arginina em homozigose possua um efeito protetor contra a carcinogenese tiroideana (OR:0,15; p<0,0001). Os dados gerados pela meta-analise demonstraram que a relacao entre o genotipo e o fenotipo originado do polimorfismo de TP5372 nao esta associada a susceptibilidade genetica ao câncer de tireoide. Palavras-chave: Polimorfismo. Gene TP5372. Câncer de tireoide. Susceptibilidade genetica. Meta-analise.