Objective To investigate the mechanism of the toxic effect of N-methyl-N-nitrosourea (MNU) on photoreceptor cell apoptosis of rat′s retina. Methods Thirty 50-day-old female Sprague-Dawley ( SD ) rats were intraperitoneally injected with MNU (60 mg/kg) and were put to death by dislocation of cervical vertebra 12, 24, 48, and 72 hours and 7 days after the injection, respectively. The photoreceptor cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and transmission electron microscope. The expression of proliferating cell nuclear antigen (PCNA), vimentin and glial fibrillary acidic protein (GFAP) was detected at different time after injection by immunohistochemical methods. Results The apoptotic index of the retina in the posterior pole was (33.6?2.3)%, (46.5?5.7)%, (20.1?5.3)%, (8.2?3.6)% and (2.5?1.3% at the 12th, 24 th, 48 th, and 72nd hour and on the 7th day, respectively, after injection. Karyopyknosis was found in most photoreceptor cells 24 hours after injection. The expression of PCNA was found in internal granular layer and between internal granular layer and choroid 24 hours after injection, reached the peak after 72 hours, and reduced obviously after 7 days. The positive expression of GFAP and vimentin was found in internal and external granular layer 24 hours after injection, reached the peak after 72 hours, and reduced obviously after 7 days. Conclusion MNU may selectively lead the photoreceptor cell apoptosis and proliferation of M?ller cells.

OBJECTIVETo evaluate and map the putative tumor suppressor loci on chromosome 5 involved in tumor progress or metastasis.

METHODSChromosome 5 of 83 patients with sporadic colorectal cancer was systemically screened. Fifteen microsatellite marker primers labeled with 3 different fluorescents were used to amplify the corresponding loci of the genome DNA. The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed with Genotyper and Genescan software.

RESULTSThe highest loss of heterozygosity (LOH) ratio was found at D5S416 (48.15%) on 5p and at D5S471 (38.71%) on 5q. The region (5q13.3 - 31), where D5S471 and 3 neighboring loci (D5S428, D5S2027 and D5S2115) reside, presented high frequent LOH.

CONCLUSIONThe deletion of APC, MCC, CTNNA1 and IL cluster in the 5q 13.3 - 31.1 area play important role in the tumorogenesis of colorectal cancer, and the expected existence of another novel tumor suppressor gene on 5p is possible.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; Colorectal Neoplasms ; genetics ; Female ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; genetics ; Middle Aged

OBJECTIVETo analyze the loss of heterozygosity (LOH) of chromosome 20 in patients with sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis.

METHODSPolymorphic microsatellite markers were analyzed in 83 colorectal cancer patients' tumor and normal DNA by PCR. PCR products were electrophoresed on an 377 DNA sequencer. Genescan 2.1 and Genotype 2.1 software were used in the LOH scanning and analysis. Comparisons between LOH frequency and clinicopathological data were performed by chi(2) test. P < 0.05 was considered statistically significant.

RESULTSThe average LOH frequency in the long arm, short arm and whole chromosome 20 was 21.1%, 26.7% and 22.8%, respectively. Chromosome 20 exhibited relatively high LOH frequency, particularly in the regions of 20p and 20q11.1-q13.1.

CONCLUSIONThere is notable genetic instability on chromosome 20 in sporadic colorectal carcinoma patients; that is, mutation on chromosome 20 is closely associated with sporadic colorectal carcinogenesis. Also, there may be tumor suppressor genes related to sporadic colorectal carcinoma near the region 20q11.1-q13.1.

Adult ; Aged ; Aged, 80 and over ; Chromosomes, Human, Pair 20 ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged