摘要
Risk assessment is a necessary technical means to protect human health and environmental safety. Traditional risk assessment based on toxicity data obtained from animal experiments was difficult to meet the need for risk assessment for a large number of chemicals due to the low throughput, long cycle, high cost and uncertainty of extrapolation to human exposure dose. The proposed risk assessment frameworks, the model of action (MOA) and the adverse outcome pathway (AOP), pointed the way for us to develop new and efficient evaluation methods. In this review, the basic concepts and contents of MOA and AOP, as well as the relationship between them, were introduced. Taking acrylamide (AA) as an example, this review briefly described the application of MOA/AOP framework in chemical risk assessment, so as to provide theoretical guidance for better application of MOA/AOP framework in chemical risk assessment.
摘要
<p><b>OBJECTIVE</b>To explore potential epigenetic biomarkers for toxic effects, tumor-related chemical prevention and biological monitor by a genome-wide screening for differential DNA methylation during human cell malignant transformation in vitro.</p><p><b>METHODS</b>The two in vitro cell transformation models included B(a)P-induced human bronchial epithelial cell introduced by H-Ras (HBER) cell transformation and simian vacuolating virus 40 small T antigen induced (SV40 ST-induced) HBER cell transformation. Methylated genes were collected by methylated DNA immunoprecipitation and whole genome amplification (MeDIP-WGA) at three time points during cell transformation which represented different transformation stage. Then, CpG island microarray was used to screen differentially methylated genes. The mRNA levels of hypermethylated genes were also observed by RT-PCR.</p><p><b>RESULTS</b>The CpG island microarray showed that the number of hypermethylated genes in HBER, HBERNT, HBERT cells were 733, 661 and 738 respectively.83 genes were hypermethylated in pre-transformed cell and transformed cell. Moreover, 25 of 83 genes were also hypermethylated in SV40 ST-transformed cell (HBERST). We further confirmed that the mRNA expression of six of these 25 genes, namely family with sequence similarity 178, member A (FAM178A), retinoic acid receptor responder (tazarotene induced) (RARRES1), ubiquitin specific peptidase 28 (USP28), Scm-like with four mbt domains 2 (SFMBT2), family with sequence similarity 59, member A (FAM59A) and nuclear receptor subfamily 4, group A, member 3 (NR4A3) were suppressed during B(a)P-induced transformation.</p><p><b>CONCLUSION</b>The abnormal hypermethylation of specific genes was a common event in the two kinds of human cell transformation models, which shed light on the study for chemical exposure monitor and tumor-related epigenetic biomarkers.</p>
Subject(s)
Humans , Biomarkers , Carcinogens, Environmental , Cell Line , Cell Transformation, Neoplastic , Genetics , CpG Islands , DNA Methylation , Epigenesis, Genetic , Gene Expression Profiling , Genome摘要
<p><b>OBJECTIVE</b>Newborns have been the focus group for most studies of cytomegalovirus infection. The objective of the study is to share some preliminary analysis on clinical manifestation differences resulting from cytomegalovirus infection in children of various age groups.</p><p><b>METHODS</b>The clinical data of 108 children with cytomegalovirus infection were retrospectively reviewed. The children were classified into three age groups: <6 months, 6-12 months and >12 months. The differences in clinical manifestations from cytomegalovirus infection among the three age groups were identified.</p><p><b>RESULTS</b>Each age group carried distinctive differences in the occurrence of hepatic damage, jaundice, pneumonia, and hematological manifestations, as well as incidence rate of malformation (p<0.05 or 0.01). The primary clinical manifestations of group<6 months old were hepatic damage(83%), pneumonia(47%) and jaundice (43%). There was a similar proportion of anicteric-hepatitis and icteric-hepatitis; however a low incidence rate of hematological disease (6%) was found in group<6 months old. The primary clinical manifestations of group 6-12 months old were hepatic damage (86%), mostly with no presence of jaundice, pneumonia (33%), and hematological disease (20%). Hepatic damage (52%) and hematological disease (33%) were leading clinical symptoms in group>12 months old where jaundice and pneumonia were rare events.</p><p><b>CONCLUSIONS</b>End-organ damage triggered by cytomegalovirus infection is related to the age of the affected children closely.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Age Factors , Cytomegalovirus Infections , Therapeutics摘要
<p><b>OBJECTIVE</b>To establish human bronchial epithelial cell lines over expressing oncogene and to investigate its application in detection of carcinogen-induced cell transformation.</p><p><b>METHODS</b>Mediated by retrovirus infection, human telomerase catalytic subunit, hTERT was introduced into immortal human bronchial epithelial cells (16HBE) and followed by introduction of the oncogenic allele H-Ras(V12), or c-Myc or empty vector, creating cell lines 16HBETR, 16HBETM and 16HBETV, respectively. Biological characteristics of these cell lines including morphology, proliferation, and chromosomal aberration were examined to access whether they were transformed. Soft agar experiment and nude mice subcutaneous injection were performed using pre-transformed 16HBE cells induced by known carcinogens, nickel sulfate (NiSO4) and 7, 8, -dihydrodiol-9, 10-epoxide benzo[a] pyrene (BPDE).</p><p><b>RESULTS</b>With detection of telomerase activity and Western blotting, the expression of target proteins was verified. Thus, the transgenic 16HBE cell lines were successfully established. Cells expressing oncogene H-Ras or c-Myc grew 30.3% or 10.4% faster than control cells. However, these cells failed to form colonies in soft agar or form tumor in nude mice. 16HBETR, 16HBETM cells obtained transformed phenotype at 5 wks, 11 wks, respectively after treatment with BPDE, which are 15 wks and 9 wks earlier than control cells 16HBETV (20 wks). Meanwhile, 16HBETR, 16HBETM cells obtained transformed phenotype at 11 wks, 14 wks, respectively after treatment with nickel sulfate, which are 21 wks and 18 wks earlier than control cells (32 wks).</p><p><b>CONCLUSION</b>With the advantage of shorter latency, transgenic human cell transformation models could be used in potent carcinogen screening and applied to chemical-carcinogenesis mechanism study.</p>
Subject(s)
Animals , Humans , Mice , 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide , Toxicity , Carcinogenicity Tests , Cell Line , Cell Transformation, Neoplastic , Metabolism , Pathology , Epithelial Cells , Gene Expression , Gene Expression Regulation , Genes, myc , Genes, ras , Mice, Inbred BALB C , Mice, Nude摘要
Objective To investigate the prevalence of nodular gastritis,duodenal ulcer before and after eradicative treatment of helicobactor pylori(Hp) infection in children with gastroscopy.Methods This was a retrospective analysis of 1 275 children,age ranging 1 to 16 years old,collected from our hospital in recent 10 years,detecting rates of before eradicative treatment and after eradicative treatment were analyzed.Gastroscopes were analyzed with regard to a possible association with the infection.Results The detecting rate(11.89%) of duodenal ulcer after eradicative treatment was lower than that(17%) before eradicative treatment(P
摘要
0.05).There was significant difference of curative effect before and after treatment of children with RAP(?2=6.74,P