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31.
The involvement of the proliferating cell nuclear antigen (PCNA) in the
process of DNA repair induced by alkylating agents or by oxidative damage
was investigated in human quiescent fibroblasts by immunofluorescence and
flow cytometry. Transition from soluble to the DNA-bound form of PCNA, was
taken as the parameter to determine its involvement in repair DNA
synthesis. Treatment with the alkylating agents methylmethane sulfonate and
N-methyl-N'-nitro-N-nitrosoguanidine resulted in the rapid and
dose-dependent increase in the nuclear binding of PCNA. Similar results
were obtained with compounds such as hydrogen peroxide or tert-butyl
hydroperoxide, which are known to induce oxidative DNA damage. Tert-butyl
hydroperoxide may also generate malondialdehyde through a reaction of lipid
peroxidation. This mutagenic and carcinogenic product has been previously
shown to form adducts with DNA. Therefore, the possibility that tert-butyl
hydroperoxide could induce DNA damage through this pathway was investigated
by incubating cells directly in the presence of malondialdehyde. Such
treatment resulted in an increase in immunofluorescence associated with
nuclear-bound PCNA. The ability of oxidative and alkylating agents to
induce the nuclear binding of PCNA was also assessed in proliferating
cells. In these conditions, treatment with hydrogen peroxide or
methylmethane sulfonate, resulted in an increase in nuclear-bound PCNA in
the G1 and in the G2 + M compartments, but not in S phase. At longer times
after treatment, PCNA immunostaining was reduced to basal levels, while an
increase in nuclear binding of p21(waf1/cip1) protein was found in
concomitance with cell-cycle arrest. These results indicate that agents
inducing DNA base alterations in vivo, promote the nuclear binding of PCNA.
These lines of evidence support the role of a PCNA-dependent reaction in
the base excision repair system.
相似文献
32.
Hansen LA; Malarkey DE; Wilkinson JE; Rosenberg M; Woychik RE; Tennant RW 《Carcinogenesis》1998,19(10):1837-1845
We previously reported that papillomas can arise from the follicular
epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow
mutation (A(vy)) of the mouse agouti gene which regulates coat color
pigmentation by acting within the micro-environment of the hair follicle
has been shown to function as a tumor promoter in the liver, we
hypothesized that it may also play a role in TGxAC skin tumorigenesis.
Endogenous agouti protein product was detected in the outer root sheath of
anagen hair follicles following plucking of the hair shaft, but not in the
interfollicular epithelium, in TGxAC mice on an FVB/N genetic background.
It was also detected in papillomas from these mice produced by
12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking.
Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line
results in an approximately 2-fold increase in papilloma development
compared with controls which did not carry the A(vy) allele following
twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition,
TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but
not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of
humoral hypercalcemia mediated by parathyroid hormone-related protein
(PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus,
we conclude that the A(vy) allele can influence the development of skin
tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic
TGxAC mice.
相似文献
33.
Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer 总被引:2,自引:0,他引:2
Davidson LA; Aymond CM; Jiang YH; Turner ND; Lupton JR; Chapkin RS 《Carcinogenesis》1998,19(2):253-257
We have developed a non-invasive method utilizing feces, containing
sloughed colonocytes, as a sensitive technique for detecting diagnostic
colonic biomarkers. In this study, we used the rat colon carcinogenesis
model to determine if changes in fecal protein kinase C (PKC) expression
have predictive value in monitoring the neoplastic process. Weanling rats
were injected with saline or azoxymethane (AOM) and 36 weeks later fecal
samples and mucosa were collected, poly A+ RNA isolated, and quantitative
RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and
zeta mRNA levels were altered by the presence of a tumor, with
tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII
expression as compared with animals without tumors. In addition,
AOM-injection increased mucosal PKC betaII mRNA expression compared with
saline controls. No effect of tumor incidence on mucosal PKC betaII
expression was observed. In contrast, fecal PKC zeta expression was
2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus
saline. Since tumor incidence exerts a reciprocal effect on fecal PKC
betaII and zeta mRNA expression, data were also expressed as the ratio
between PKC betaII and zeta. The isozyme ratio was strongly related to
tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25,
animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that
the expression of fecal PKC betaII and zeta may serve as a noninvasive
marker for development of colon tumors. A sensitive technique for the
detection of colon cancer is of importance since early diagnosis can
substantially reduce mortality.
相似文献
34.
Lambert SB Morgan ML Riddell MA Andrews RM Kelly HA Leydon JA Catton MC Lynch PA Gercovich DK Lester RA Carnie JA Rouch GJ 《The Medical journal of Australia》2000,173(9):467-471
OBJECTIVES: To describe an outbreak of measles in Victoria. DESIGN: Case series with cases identified through enhanced passive surveillance and outbreak-related active surveillance. SETTING: State of Victoria, 1999. MAIN OUTCOME MEASURES: Number of cases; epidemiological links and patterns of transmission; patient demographic features and vaccination status; complications. RESULTS: 75 cases were identified (74 laboratory-confirmed; and one epidemiologically linked to a laboratory-confirmed case), with onset between 11 February and 2 May 1999. The first case was in a 21-year-old woman who had recently holidayed in Bali and worked at a large cinema complex in Melbourne. Sixteen cases occurred in people who had contact with the index case at the cinema on one evening. The outbreak spread to regional Victoria and South Australia. Median age of patients was 22 years; 64 (85%) were born between 1968 and 1981, with only one patient in the age group targeted by the primary school component of the 1998 Australian Measles Control Campaign; this child had not been vaccinated. More than a third of patients (28) were hospitalised (total, 97 inpatient days), and five were healthcare workers. CONCLUSIONS: This outbreak was caused by international importation of measles virus. It highlights the change in epidemiology of measles in Australia, from a disease of childhood to one predominantly affecting young adults. A strong two-dose childhood vaccination program, vigilant surveillance, and rapid response to outbreaks will continue to be the basis of measles control, but better protection for young adults should be considered. 相似文献
35.
宫颈病变液基细胞学筛查与组织病理学对照观察 总被引:5,自引:1,他引:5
目的 探讨液基薄层细胞学(ThinPrepCytologyTest, TCT)技术在妇科门诊人群宫颈病变筛查的准确性。方法 回顾性分析10 980例TCT,与组织学对比观察。结果 TCTLSIL以上阳性率45. 7% ( 373 /817),组织学检查阳性率50. 1% ( 409 /817 ),两者统计学比较无显著性差异(P>0. 05 )。TCT诊断符合率LSIL75. 8% (191 /252),HSIL98. 1% (101 /103),SCC90. 9% (10 /11),AC85. 7% (6 /7)。鳞状上皮内病变诊断符合率HSIL与LSIL统计学比较有显著性差异(P<0. 01)。结论 液基细胞学检查是宫颈癌早期筛查的有效手段,加强制片技术及诊断质量控制对提高诊断的准确性有重要意义。 相似文献
36.
37.
奇乳海参中两个具有抗真菌活性的三萜皂苷 总被引:2,自引:0,他引:2
目的:研究奇乳海参体内的化学成分,寻找结构新颖具有抗真菌活性的三萜皂苷类成分。方法:应用多种色谱分离技术对奇乳海参体内的化学成分进行分离纯化,根据化合物的理化性质,波谱数据及化学方法鉴定其结构。结果:分离得到2个三萜皂苷化合物,分别为axilogoside A(1)和holothurin B(2),并对其抗真菌活性进行了研究(4≤MIC80≤16μg·mL^-1)。结论:化合物1为一新的三萜皂苷化舍物,化合物2为首次从奇乳海参中分离得到,它们均显示一定的抗真菌活性。 相似文献
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