Standardized methods for bone marrow micronucleus test in rodents and historical data collection / 药物评价研究

In vivo Mammalian Bone Marrow Micronucleus Test is included in the standard battery genotoxicity testing,with great application prospects in medicine,public health,food and drug safety evaluation fields.Establishing standardized experimental methods and conditions in GLP condition and accumulating a certain range of background data could effectively ensure the reliability of the test system,and also provide strong basis to support the experimental data.We herein summarized the background data of mouse and rat bone marrow micronucleus tests performed from 2007 to 2015,to expound the standardized data collection method for rodent animal bone marrow micronucleus test.

Incidence of malignancy and clonal chromosomal abnormalities in Fanconi anemia.

Background: Fanconi anemia (FA) is an autosomal recessive, cancer susceptibility disorder characterized by diverse clinical features, such as short stature, skeletal or skin abnormalities, progressive bone marrow (BM) failure, and increased risk of malignancies. Clonal chromosomal abnormalities are frequently reported in FA patients transformed to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aim: To study the incidence of malignancy and clonal chromosomal abnormalities in FA patients. Materials and Methods: Thirty-eight clinically diagnosed FA patients were studied at the time of diagnosis and the patients were followed-up for a maximum of 28 months at 3-month intervals. The median duration of follow-up of these patients was 19.8 months. Chromosomal breakage investigation using mitomycin C (MMC)- and diepoxybutane (DEB)-induced peripheral blood cultures were stimulated with phytohemagglutinin. Cytogenetic study was done on the BM cells to detect clonal chromosomal aberrations. Results: Eleven (28.95%) out of 38 patients developed malignancies, including 6 (54.54%) MDS, 4 (36.36%) AML, and 1 (2.63%) squamous cell carcinoma. The clonal chromosomal abnormalities were detected in 5 (45.45%) FA patients who developed malignancies and the type of chromosomal abnormality detected were monosomies 5, 7, trisomy 10, dup(1)(q12-q24), and inv(7)(p11pter). Conclusion: The FA patients have a high risk of developing malignancies, and clonal chromosomal abnormalities play an important role in the prognosis of the disease. Therefore, FA patients need to be followed-up at regular intervals for early diagnosis and optimal management of the disease.

A Case of Fanconi Anemia Diagnosed by a Chromosome Breakage Test with Skin Fibroblasts / 대한혈액학회지

Fanconi anemia is an autosomal recessive disease that's characterized by congenital anomalies, defective hematopoiesis and a high risk of developing acute myeloid leukemia and certain solid tumors. The clinical phenotype is extremely variable; therefore, the diagnosis is frequently delayed until the pancytopenia appears. Chromosomal instability, especially on exposure to an alkylating agent, may be seen in affected patients and it is the basis for a diagnostic test. This cellular phenotype can be demonstrated in cultured T cells, B cells, fibroblasts and fetal cells cultured from both amniotic fluid and chorionic villi. But somatic mosaicism may make the diagnosis of Fanconi anemia difficult because of inconclusive chromosome breakage studies. If the test is negative in lymphocytes and yet the clinical setting is highly suspicious, then the skin fibroblasts must be assessed. Because skin fibroblasts are somatic cells, a definitive test can be performed on primary skin fibroblasts. In this report we describe a case of Fanconi anemia that was diagnosed with the use of cultured skin fibroblasts, and this was despite the normal breakage studies in the peripheral blood.

Teste dos micronúcleos: um biomarcador de dano genotóxico em células descamadas da mucosa bucal / Micronucleus assay: a biomarker of genotoxic damage in exfoliated oral mucosa cells

O objetivo deste trabalho é fazer uma revisão de literatura a respeito do ensaio dos micronúcleos, explicando o seu significado e sua aplicação em células esfoliadas da mucosa bucal. Micronúcleo (MN) é um núcleo acessório, originado a partir de fragmentos de cromossomo ou de cromossomos inteiros que não são incluídos no núcleo principal durante a mitose. MNs surgem por alterações genéticas espontâneas ou são induzidos por agentes genotóxicos. A análise dos micronúcleos tem sido utilizada como uma ferramenta importante de biomonitoramento de populações. Estudos demonstram que consumidores de fumo e álcool, assim como grupos expostos a determinados agentes em função de sua ocupação ou estilo de vida apresentam um elevado número de MNs nas células bucais esfoliadas.

The aim of this study is to summarise the literature on micronucleus assay, explaining its meaning and its application in exfoliated oral mucosal cells. Micronuclei (MN) is an extra nuclei, originated from chromosome fragments or whole chromosomes that are not included in the main nuclei during mitosis. MNs arise from spontaneous genetic damage or are induced by genotoxic agents. MN analysis has been used as an important tool to biomonitore populations exposed to life-style agents. Studies demonstrate that tobacco and alcohol users, as well as occupationally exposed groups present increased number of MNs in exfoliated oral mucosa cells. Despite the fact that the role of MN frequency has not yet been fully understood, the MNs assay is considered to be an effective biomarker of oral squamous cell carcinoma risk factors effects.

Antagonism of Chinese medicine herbals on chromsome breakage induced by Bleomycin / 吉林大学学报(医学版)

Objective To study the antagonsim of Chinese medicine herbals on the chromsome breakage induced by Bleomycin(BLM),which was composed of ginseng,cortex acanthopanasia radices(CAR),pachyna cocos Fr.and angelica at certain concentration.Methods The mutagen sensitivety test was used to detect the effect of BLM on chromatid breaks per cell from peripheral blood lymphocytes of 20 healthy subjects.And the infuence of Chinese medical herbals on the stability of chromsome was studied.50 cells per sample were observed under microscope and then the average b/c value(chromatid breaks per cell) of every group was calculated.The all b/c values were analyzed by statistical method.Results There was obvious difference of the b/c value between BLM group and negative group(P