Biomedical subjects

L Shao

Publications and source records attributed to L Shao.

At least 19 recordsLinked to original sources

PubMed2006

Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate.

Mood stabilizing drugs lithium and valproate are the most commonly used treatments for bipolar disorder. Previous studies in our laboratory indicate that chronic treatment with lithium and valproate inhibits oxidative damage in primary cultured rat cerebral cortical cells. Glutathione, as the major antioxidant in the brain, plays a key role in defending against oxidative damage. The purpose of this study was to determine the role of glutathione in the neuroprotective effects of lithium and valproate against oxidative damage. We found that chronic treatment with lithium and valproate inhibited reactive oxygen metabolite H(2)O(2)-induced cell death in primary cultured rat cerebral cortical cells, while buthionine sulfoximine, an inhibitor of glutathione rate-limiting synthesis enzyme glutamate-cysteine ligase, reduced the neuroprotective effect of lithium and valproate against H(2)O(2)-induced cell death. Further, we found that chronic treatment with lithium and valproate increased glutathione levels in primary cultured rat cerebral cortical cells and that the effects of lithium and valproate on glutathione levels were dose-dependent in human neuroblastoma SH-SY5Y cells. Chronic treatment with lithium and valproate also increased the expression of glutamate-cysteine ligase in both rat cerebral cortical cells and SH-SY5Y cells. In addition, chronic treatment with other mood stabilizing drugs lamotrigine and carbamazepine, but not antidepressants desipramine and fluoxetine, increased both glutathione levels and the expression of glutamate-cysteine ligase in SH-SY5Y cells. These results suggest that glutathione plays an important role in the neuroprotective effects of lithium and valproate, and that glutathione may be a common target for mood stabilizing drugs.

Animals↗

PubMed2006

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders.

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders.

Antidepressive Agents↗

PubMed2006

Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families.

Proinflammatory and immunoregulatory products from C3 play a major role in phagocytosis, respiratory burst, and airways inflammation. C3 is critical in adaptive immunity; studies in mice deficient in C3 demonstrate that features of asthma are significantly attenuated in the absence of C3. To test the hypothesis that the C3 gene on chromosome 19p13.3-p13.2 contains variants associated with asthma and related phenotypes, we genotyped 25 single nucleotide polymorphism (SNP) markers distributed at intervals of approximately 1.9 kb within the C3 gene in 852 African Caribbean subjects from 125 nuclear and extended pedigrees. We used the multiallelic test in the family-based association test program to examine sliding windows comprised of 2-6 SNPs. A five-SNP window between markers rs10402876 and rs366510 provided strongest evidence for linkage in the presence of linkage disequilibrium for asthma, high log[total IgE], and high log[IL-13]/[log[IFN-gamma] in terms of global P-values (P = 0.00027, 0.00013, and 0.003, respectively). A three-SNP haplotype GGC for the first three of these markers showed best overall significance for the three phenotypes (P = 0.003, 0.007, 0.018, respectively) considering haplotype-specific tests. Taken together, these results implicate the C3 gene as a priority candidate controlling risk for asthma and allergic disease in this population of African descent.

Asthma↗

PubMed2006

Electrolytic degradation of biorefractory organics and ammonia in leachate from bioreactor landfill.

Electrochemical oxidation was applied to treat the effluent from bioreactor landfill with leachate recirculation, characterised as poor biodegradability and high NH3-N concentration. In this study, the effluent was electrolysed in a batch reactor with Ti/TiO2-IrO2-RuO2 anode and stainless steel cathode. The oxidation of dissolved organic matter (DOM) during electrolysis was evaluated based on the evolution of molecular weight grade, hydrophilic fractionation (humic acid, fulvic acid and hydrophilic fractions), specific ultraviolet absorbance (SUVA254) and AOX. The impact of the initial NH3-N concentration on the oxidation was discussed. The results showed that at a current density of 100 mA/cm2, electrolysis time of 1.5 h and electrode gap of 1 cm, NH3-N with an initial concentration of 1.2 g/L could be completely eliminated and 56% of COD with an initial concentration of 1.2 g/L could be removed, which illustrated that the electrolysis-produced chlorine preferentially oxidised ammonia. The electrolysis mainly resulted in the degradation of humic substances and other high molecular DOM, followed by the increase of BOD/COD ratio and decline of SUVA254 of the leachate. The current efficiencies for COD and ammonia oxidation gradually decreased during the electrolysis, with the latter obviously higher than the former. At the optimal electrolysis time of 1.5 h, NH3-N could be totally removed and the BOD/COD ratio could be enhanced to 0.3, which was also favourable to control the AOX at a reasonable level.

Ammonia↗

PubMed2004

Detection of the differentially expressed gene IGF-binding protein-related protein-1 and analysis of its relationship to fasting glucose in Chinese colorectal cancer patients.

IGF-binding protein-related protein-1 (IGFBP-rP1) is a member of the IGF axis. In our previous work, we separated cDNA fragments of IGFBP-rP1 from colonic adenocarcinoma and normal mucosa cDNA subtraction libraries. In this study, we compared the expression of IGFBP-rP1 by semi-quantitative RT-PCR and immunohistochemistry among colorectal cancer, adenoma, normal tissue adjacent to cancer site, and normal tissue. Associations between IGFBP-rP1 and plasma glucose were further explored. We found that the mRNA level of IGFBP-rP1 was highest in cancer, moderate in adenoma and tissue adjacent to the cancer site and lowest in normal tissue (P<0.05). A significant difference was found in the immunoreactivity of IGFBP-rP1 between paired normal and cancer tissue (P<0.05). Tumor samples with upregulated expression of IGFBP-rP1 in invading tumor cells showed an increased frequency of metastasis to the lymph node, an increased depth of infiltration and stronger staining of IGFBP-rP1 compared with other samples (P<0.05). The fasting glucose level was significantly correlated with the staining of IGFBP-rP1 in cancer tissue (Spearman's rho=0.4, P<0.000). Thus, we concluded overexpression of IGFBP-rP1 might play an important role in the initiation and promotion of colorectal cancer. IGFBP-rP1 expression may also be associated with fasting glucose level and the presence of diabetes mellitus.

Adenocarcinoma↗

PubMed2003

O-fucose modifications of epidermal growth factor-like repeats and thrombospondin type 1 repeats: unusual modifications in unusual places.

Recent discoveries revealing that carbohydrate modifications play critical roles in a wide variety of biological processes have brought wide recognition to the field of glycobiology. Growing attention has focused on the function of unusual O-linked carbohydrate modifications such as O-fucose. O-fucose modifications have been described in several different protein contexts, including epidermal growth factor-like repeats and thrombospondin type 1 repeats. The O-fucose modifications on thrombospondin type 1 repeats have only recently been described, but the site of modification occurs in a region proposed to play a role in cell adhesion. O-fucose modifications on epidermal growth factor-like repeats have been described as important players in several signal transduction systems. For instance, Notch, a cell-surface signaling receptor required for many developmental events, bears multiple O-fucose saccharides on the epidermal growth factor-like repeat of its extracellular domain. The O-fucose moieties serve as a substrate for the beta1,3 N-acetylglucosaminyltransferase activity of Fringe, a known modifier of Notch function. The alteration of O-fucose structures by Fringe influences the ability of Notch ligands to activate the receptor and provides a means to regulate Notch signaling. Thus, O-fucose and Fringe provide a clear example of how carbohydrate modifications can have direct functional consequences on the proteins they modify.

Animals↗

PubMed2002

Subluminous phase velocity of a focused laser beam and vacuum laser acceleration.

It has been found that for a focused laser beam propagating in free space, there exists, surrounding the laser beam axis, a subluminous wave phase velocity region. Relativistic electrons injected into this region can be trapped in the acceleration phase and remain in phase with the laser field for sufficiently long times, thereby receiving considerable energy from the field. Optics placed near the laser focus are not necessary, thus allowing high intensities and large energy gains. Important features of this process are examined via test particle simulations. The resulting energy gains are in agreement with theoretical estimates based on acceleration by the axial laser field.

Journal Article↗

PubMed2002

Hyaluronan metabolism in rat tail skin following blockage of the lymphatic circulation.

This study was undertaken to explore the effects of lymphatic blockage on the metabolism of hyaluronan in the skin. In initial experiments, [3H] hyaluronan was injected subcutaneously into the tail skin of rats that either had no surgical intervention (control) or into those that had their lymphatic drainage blocked two hours earlier (acute lymphedema) or after the lymphatics had been blocked for three months (chronic lymphedema). The removal of tritiated hyaluronan from the injection sites was determined by the appearance of [3H] in the plasma. The results showed that the clearance of injected hyaluronan was delayed in rats with lymphatic blockage. The half- life of injected hyaluronan in the controls was approximately 70-75 hr, compared with approximately 105-110 hr in the lymph blocking rats. The levels of radioactivity in the plasma from rats with both acute and chronically blocked lymphatics were lower than that of control rats during the entire follow up period. In addition, biochemical analysis revealed that there was a significant increased amount of hyaluronan in the tail skin three months after lymphatic blocking. These results suggest that lymph absorption is an important factor in the transport of hyaluronan from the interstitium. Blockage of regional draining lymphatics likely impairs the catabolism of hyaluronan, which stagnates in skin tissue.

Animals↗

PubMed2001

Iridals are a novel class of ligands for phorbol ester receptors with modest selectivity for the RasGRP receptor subfamily.

Since 1990, the National Cancer Institute has performed extensive in vitro screening of compounds for anticancer activity. To date, more than 70 000 compounds have been screened for their antiproliferation activities against a panel of 60 human cancer cell lines. We probed this database to identify novel structural classes with a pattern of biological activity on these cell lines similar to that of the phorbol esters. The iridals form such a structural class. Using the program Autodock, we show that the iridals dock to the same position on the C1b domain of protein kinase C delta as do the phorbol esters, with the primary hydroxyl group of the iridal at the C3 position forming two hydrogen bonds with the amide group of Thr12 and with the carbonyl group of Leu 21 and the aldehyde oxygen of the iridal forming a hydrogen bond with the amide group of Gly23. Biological analysis of two iridals, NSC 631939 and NSC 631941, revealed that they bound to protein kinase C alpha with K(i) values of 75.6 +/- 1.3 and 83.6 +/- 1.5 nM, respectively. Protein kinase C is now recognized to represent only one of five families of proteins with C1 domains capable of high-affinity binding of diacylglycerol and the phorbol esters. NSC 631939 and NSC 631941 bound to RasGRP3, a phorbol ester receptor that directly links diacylglycerol/phorbol ester signaling with Ras activation, with K(i) values of 15.5 +/- 2.3 and 41.7 +/- 6.5 nM, respectively. Relative to phorbol 12,13-dibutyrate, they showed 15- and 6-fold selectivity for RasGRP3. Both compounds caused translocation of green fluorescent protein tagged RasGRP3 expressed in HEK293 cells, and both compounds induced phosphorylation of ERK1/2, a downstream indicator of Ras activation, in a RasGRP3-dependent fashion. We conclude that the iridals represent a promising structural motif for design of ligands for phorbol ester receptor family members.

Acrolein↗

PubMed2001

Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.

Increased expression of intracellular thioredoxin has been implicated in the inhibition of apoptosis and in a decrease in the sensitivity of the malignancies to drug-induced apoptosis. In the present studies, we analyzed expression of thioredoxin in samples from 28 children with T-cell acute lymphoblastic leukemia and analyzed their sensitivity toward inhibition of thioredoxin expression. Thioredoxin was expressed in variable amounts. Higher expression was associated with higher WBC counts. Exogenously added thioredoxin stimulated proliferation of clonogenic cells among the T-cell acute lymphoblastic leukemia samples expressing relatively lower levels of intracellular thioredoxin, whereas there was no effect on the clonogenic cells expressing high levels of thioredoxin. In addition, there was differential sensitivity of the leukemia clonogenic cells toward 1-methylpropyl 2-imidazolyl disulfide, an inhibitor of thioredoxin expression, as compared with normal hematopoietic progenitors. This suggests the possibility of using this approach for treatment. Because overexpression of thioredoxin is associated with resistance to many anticancer drugs, the inhibition of thioredoxin expression may overcome this drug resistance and probably sensitize leukemia cells to other chemotherapeutic agents.

Antineoplastic Agents↗

PubMed2001

Beyond butadiene II: thermal isomerization of the [2 + 2] photodimer of an all-trans tetraene, (R)-4,4abeta,5,6,10a-hexahydro-10abeta-methyl-2(3H)-methyleneanthracene, to a 16-membered [8 + 8] cycle.

Enthalpies of stabilization of polyenyl radicals of increasing order previously obtained by thermal geometrical isomerization are applied to the ethylene-cyclobutane paradigm. Progressively lower enthalpies of activation for thermal cyclodimerization and its reverse, cycloreversion, are predicted and realized. Photochemical dimerization at -75 degrees C of the optically pure tetraene of the title (1) at the semicyclic double bond produces in the main only one (4-axx) of the three allowed cyclobutanes (4), to which the tentative configuration anti-exo,exo is assigned. Equilibration among the three cyclobutanes (4), a slower rearrangement to a thermodynamically considerably more stable, [8 + 8] cyclohexadecahexaene (16), and a surprisingly slow fragmentation to 1 are studied kinetically between -42.3 and -8.2 degrees C. Cycloreversion of the dimer 16 to monomer 1 occurs in the range 60.4-86.6 degrees C (DeltaH = 31.7 kcal mol(-1), DeltaS = +10.8 cal mol(-1) K(-1)). The ratio of the rates of stereomutation and cycloreversion is significantly larger in these 1,2-dihexatrienylcyclobutanes than in two less strongly stabilized, previously published examples. The possible extension of Doubleday's calculational finding of entropic control of products from cyclobutane is considered.

Journal Article↗

PubMed2001

Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase.

The O-fucose modification is found on epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-Fucose glycans play important roles in ligand-induced receptor signaling. For example, elongation of O-fucose on Notch by the beta1,3-N-acetylglucosaminyltransferase Fringe modulates the ability of Notch to respond to its ligands. The enzyme that adds O-fucose to epidermal growth factor-like repeats, GDP-fucose protein O-fucosyltransferase (O-FucT-1), was purified previously from Chinese hamster ovary (CHO) cells. Here we report the isolation of a cDNA that encodes human O-FucT-1. A probe deduced from N-terminal sequence analysis of purified CHO O-FucT-1 was used to screen a human heart cDNA library and expressed sequence tag and genomic data bases. The cDNA contains an open reading frame encoding a protein of 388 amino acids with a predicted N-terminal transmembrane sequence typical of a type II membrane orientation. Likewise, the mouse homolog obtained from an expressed sequence tag and 5'-rapid amplification of cDNA ends of a mouse liver cDNA library encodes a type II transmembrane protein of 393 amino acids with 90.4% identity to human O-FucT-1. Homologs were also found in Drosophila and Caenorhabditis elegans with 41.2 and 29.4% identity to human O-FucT-1, respectively. The human gene (POFUT1) is on chromosome 20 between PLAGL2 and KIF3B, near the centromere at 20p11. The mouse gene (Pofut1) maps near Plagl2 on a homologous region of mouse chromosome 2. POFUT1 gene transcripts were expressed in all tissues examined, consistent with the widespread localization of the modification. Expression of a soluble form of human O-FucT-1 in insect cells yielded a protein of the predicted molecular weight with O-FucT-1 kinetic and enzymatic properties similar to those of O-FucT-1 purified from CHO cells. The identification of the gene encoding protein O-fucosyltransferase I now makes possible mutational strategies to examine the functions of the unusual O-fucose post-translational modification.

Amino Acid Sequence↗

PubMed2001

Complex regulation of human inducible nitric oxide synthase gene transcription by Stat 1 and NF-kappa B.

The human inducible nitric oxide synthase (hiNOS) gene is expressed in several disease states and is also important in the normal immune response. Previously, we described a cytokine-responsive enhancer between -5.2 and -6.1 kb in the 5'-flanking hiNOS promoter DNA, which contains multiple nuclear factor kappa beta (NF-kappa B) elements. Here, we describe the role of the IFN-Jak kinase-Stat (signal transducer and activator of transcription) 1 pathway for regulation of hiNOS gene transcription. In A549 human lung epithelial cells, a combination of cytokines tumor necrosis factor-alpha, interleukin-1 beta, and IFN-gamma (TNF-alpha, IL-1 beta, and IFN-gamma) function synergistically for induction of hiNOS transcription. Pharmacological inhibitors of Jak2 kinase inhibit cytokine-induced Stat 1 DNA-binding and hiNOS gene expression. Expression of a dominant-negative mutant Stat 1 inhibits cytokine-induced hiNOS reporter expression. Site-directed mutagenesis of a cis-acting DNA element at -5.8 kb in the hiNOS promoter identifies a bifunctional NF-kappa B/Stat 1 motif. In contrast, gel shift assays indicate that only Stat 1 binds to the DNA element at -5.2 kb in the hiNOS promoter. Interestingly, Stat 1 is repressive to basal and stimulated iNOS mRNA expression in 2fTGH human fibroblasts, which are refractory to iNOS induction. Overexpression of NF-kappa B activates hiNOS promoter-reporter expression in Stat 1 mutant fibroblasts, but not in the wild type, suggesting that Stat 1 inhibits NF-kappa B function in these cells. These results indicate that both Stat 1 and NF-kappa B are important in the regulation of hiNOS transcription by cytokines in a complex and cell type-specific manner.

Binding Sites↗

PubMed2001

The peritrophic matrix of hematophagous insects.

The peritrophic matrix (PM) is an extracellular envelope that lines the digestive tract of most insects. It is thought to play key roles in protecting insects from pathogens and facilitating digestion. Until recently, little information was available on the molecular composition of the PM. This review summarizes recent progress in the study of the PM from hematophagous insects, with emphasis on molecular and physiological aspects. Topics discussed include the presence of chitin and protein diversity in the PM, cloning and characterization of genes encoding PM proteins, PM permeability, and the role of the PM as a barrier for pathogens.

Animals↗

PubMed2001

The role of epithelial cells in immune regulation in the gut.

A variety of mechanisms contribute to the ability of the gut to either react or remain tolerant to antigens present in the intestinal lumen. Intestinal epithelial cells can control the uptake, transmission and presentation of luminal antigens through an astonishingly diverse set of pathways. Antigens can cross the epithelial barrier via non-specific pinocytotic, specific receptor mediated, or intracellular/paracellular bypass pathways. The differential processing and presentation by a variety of restriction elements may result in the activation of functionally distinct target cell populations which have the capacity to regulate the predominant trend of immune unresponsiveness within the gut.

Animals↗

PubMed2001

ARPP-16/ARPP-19: a highly conserved family of cAMP-regulated phosphoproteins.

ARPP-16 and ARPP-19 are closely related cAMP-regulated phosphoproteins that were initially discovered in mammalian brain as in vitro substrates for protein kinase A (PKA). ARPP-16 is enriched in dopamine-responsive medium spiny neurons in the striatum, while ARPP-19 is ubiquitously expressed. ARPP-19 is highly homologous to alpha-endosulfine and database searches allowed the identification of novel related proteins in D. melanogaster, C. elegans, S. mansoni and yeast genomes. Using isoform-specific antibodies, we now show that ARPP-19 is composed of at least two differentially expressed isoforms (termed ARPP-19 and ARPP-19e/endosulfine). All ARPP-16/19 family members contain a conserved consensus site for phosphorylation by PKA (RKPSLVA in mammalian ARPP-16 and ARPP-19), and this site was shown to be efficiently phosphorylated in vitro by PKA. An antibody that specifically recognized the phosphorylated form of ARPP-16/19/19e was used to examine the phosphorylation of ARPP-16/19 family members in intact cells. In striatal slices, the phosphorylation of ARPP-16 was increased in response to activation of D(1)-type dopamine receptors, and decreased in response to activation of D(2)-type dopamine receptors. In non-neuronal cells, ARPP-19 was highly phosphorylated in response to activation of PKA. These results establish that ARPP-16/19 proteins constitute a family of PKA-dependent intracellular messengers that function in all cells. The high levels of ARPP-16 in striatal neurons and its bi-directional regulation by dopamine suggest a specific role in dopamine-dependent signal transduction. The conservation of this protein family through evolution suggests that it subserves an important cellular function that is regulated by PKA.

Amino Acid Sequence↗

PubMed2001

Expression of matrix metalloproteinase-2, -9, -14, and tissue inhibitors of metalloproteinase-1, -2, -3 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy.

The extracellular matrix proteolytic machinery has long been recognized as one of the most important mechanisms for regulating trophoblast invasion. Matrix metalloproteinases (MMPs) are a group of proteases involved in this process, and their activities are regulated by tissue inhibitors of MMPs (TIMPs). In this study, we collected rhesus monkey uteri on Days 12, 18, and 26 of pregnancy and examined the mRNA expression of MMP-2, -9, -14, and TIMP-1, -2, -3, as well as the activities of MMP-2 and -9 by using in situ hybridization and gelatin zymography, respectively. The results showed that MMP-2 and -9 were expressed earlier than MMP-14 and TIMPs in the pregnant endometrium. MMP-14 and TIMP-2 mRNAs appeared in perivascular decidual cells earlier than MMP-2 mRNA. On Day 26 of pregnancy, placental villi expressed little MMP-2, -14, and TIMP transcripts but abundant MMP-9 mRNA. Furthermore, MMP-2, -9, -14, and TIMP-1, -2, -3 were highly expressed on the fetal-maternal border but were absent in the myometrium. TIMP-3 mRNA in the endometrium was specifically localized to some cells lining the outer membrane of several groups of arterioles. Combined with the results obtained by gelatin zymography, we found that active MMP-2 existed in the endometrium throughout these three phases, while MMP-9 showed considerable activities only on Days 18 and 26 of pregnancy. The data suggest key roles for MMP-2 and -9 in invasion of trophoblast cells into the endometrium and the development of the placenta and might indicate that these processes are regulated by MMP-14 and TIMP-1, -2, and -3.

Animals↗

PubMed2001

Mutagen sensitivity and p53 expression in colorectal cancer in China.

OBJECTIVE: This study was designed to investigate DNA damage and/or repair capability, non-random chromatid breakage, and p53 expression in patients with colorectal cancer. METHODS: The bleomycin sensitivity assay was used in a case-control study to compare the DNA damage repair system between colorectal cancer patients and controls. G-banding was used to search for non-random chromatid breaks. Immunocytochemistry was used to investigate p53 expression in tumour tissues and adjacent normal tissues. RESULTS: It was found that cases typically had a higher number of chromosome breaks than controls (0.84 v 0.69 breaks/cell, p<0.01). After correction by sex and age, the difference was still significant (F=4.38, p<0.05). The correlation coefficient between mutagen sensitivity and age was 0.31(p<0.05) in controls and 0.18 (p>0.05) in cases. The ratio of odds ratios among bleomycin resistant, sensitive, and hypersensitive classes was 1:2.31:3.85. Overexpression of p53 was detected in 25 of 47 tumour tissues independent of tumour stage. Cases who had a family history of cancer were susceptible to the p53 aberration (p<0.05). Chromosomes 1p, 5q, and 14q were susceptible to breakage in patients with colorectal cancer. CONCLUSION: Patients with colorectal cancer show increased bleomycin induced chromatid breaks and may have minor DNA repair deficiencies. p53 aberration is an early event in the development of colorectal cancer, but no definite correlation is found between p53 overexpression and mutagen sensitivity.

Adolescent↗