Biomedical subjects

J S Morris

Publications and source records attributed to J S Morris.

At least 19 recordsLinked to original sources

PubMed2000

Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer.

BACKGROUND: Selenium and alpha-tocopherol, the major form of vitamin E in supplements, appear to have a protective effect against prostate cancer. However, little attention has been paid to the possible role of gamma-tocopherol, a major component of vitamin E in the U.S. diet and the second most common tocopherol in human serum. A nested case-control study was conducted to examine the associations of alpha-tocopherol, gamma-tocopherol, and selenium with incident prostate cancer. METHODS: In 1989, a total of 10,456 male residents of Washington County, MD, donated blood for a specimen bank. A total of 117 of 145 men who developed prostate cancer and 233 matched control subjects had toenail and plasma samples available for assays of selenium, alpha-tocopherol, and gamma-tocopherol. The association between the micronutrient concentrations and the development of prostate cancer was assessed by conditional logistic regression analysis. All statistical tests were two-sided. RESULTS: The risk of prostate cancer declined, but not linearly, with increasing concentrations of alpha-tocopherol (odds ratio (highest versus lowest fifth) = 0.65; 95% confidence interval = 0.32--1.32; P(trend) =.28). For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth (P:(trend) =.002). The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth (P(trend) =.27). Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high. CONCLUSIONS: The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium.

Aged↗

PubMed2000

Inhibition of the calcium-dependent tyrosine kinase (CADTK) blocks monocyte spreading and motility.

Freshly isolated peripheral blood monocytes lack focal adhesion kinase (p125(FAK)) but activate a second member of this kinase family, calcium-dependent tyrosine kinase (CADTK; also known as Pyk2/CAKbeta/RAFTK/FAK2), upon adhesion or stimulation with chemokines. To study the role of CADTK in monocyte adherence and motility, we performed immunocytochemical localization that showed CADTK at the leading edge and ruffling lamellipodial structures in freshly isolated, adhered human monocytes. We next introduced CADTK/CAKbeta-related non-kinase (CRNK), the C-terminal noncatalytic domain of CADTK, into monocytes by electroporation and showed that it inhibited CADTK autophosphorylation. Introduction of the fusion protein glutathione S-transferase (GST)-CRNK also reduced (i) cell spreading, as reflected in a reduced cell area 30 min after adhesion, (ii) adhesion-induced phosphotyrosine increases and redistribution into lamellipodia, and (iii) adhesion-induced extracellular signal-regulated protein kinase (ERK) activation. In control experiments, introduction of GST or GST-C3 transferase (an inhibitor of RhoA GTPase activity) by electroporation did not affect these parameters. Monocytes adhered in the presence of autologous serum were highly motile even after introduction of GST (83% motile cells). However, only 26% of monocytes with introduced GST-CRNK were motile. In contrast, GST-CRNK-treated monocytes were fully capable of phagocytosis and adhesion-induced cytokine gene induction, suggesting that CADTK is not involved in these cellular activities and that GST-CRNK introduction does not inhibit global monocyte functions. These results suggest that CADTK is crucial for the in vitro monocyte cytoskeletal reorganization necessary for cell motility and is likely to be required in vivo for recruitment to sites of inflammation.

Cell Adhesion↗

PubMed2000

Histopathological survey of neoplasms in flat-coated retrievers, 1990 to 1998.

Over the period from March 1990 to December 1998, veterinary surgeons in general practice were invited to submit tissues suspected of being neoplastic which had been removed from flat-coated retrievers. When possible, pedigree details were obtained from the owners. In addition, data were collected from flat-coated retrievers known to have suffered from a neoplastic condition and for which a histopathological report was available. A total of 1023 submissions was obtained from 782 dogs. These included 165 non-neoplastic lesions (16 per cent), 447 benign samples (44 per cent) and 411 malignant samples (40 per cent). Soft tissue sarcomas accounted for 55 per cent of the malignant samples (26 per cent of all tumour samples and 22 per cent of all submissions) with 63 per cent of them being diagnosed as undifferentiated. Carcinomas accounted for 20 per cent of malignant samples (8 per cent of all submissions). Of the benign tumours, cutaneous histiocytoma was the most common diagnosis (48 per cent of benign tumours, 25 per cent of all tumours and 21 per cent of all submissions).

Animals↗

PubMed2000

Neural responses associated with cue evoked emotional states and heroin in opiate addicts.

Ten male opiate addicts, who were current heroin injectors, underwent positron emission tomographic (PET) scanning during exposure to a sequence of six alternating drug related and neutral video cues, on two occasions. After the second scan, each subject received heroin or placebo using a randomised single-blind procedure. This design allowed the investigation of patterns of brain activity during a range of self-reported cue evoked emotional states, both in the presence and absence of heroin. Self-reports of 'urge to use' correlated strongly with increased regional blood flow (rCBF) in the inferior frontal and orbitofrontal cortex target regions of the mesolimbic dopaminergic system, implicated in conditioning and reward. 'Urge to use' was also associated with highly significant increased rCBF in the right pre-cuneus, an area associated with episodic memory retrieval, and in the left insula, implicated in the processing of the emotional components of stimuli. Self-reports of feeling 'high' correlated with rCBF activation in the hippocampus, an area relevant to the acquisition of stimulus-associated reinforcement.

Adult↗

PubMed2000

Measurement of low levels of arsenic exposure: a comparison of water and toenail concentrations.

A study was conducted to evaluate toenail arsenic concentrations as a biologic marker of drinking water arsenic exposure. Study subjects were controls in a US population-based case-control study of nonmelanoma skin cancer, randomly selected from drivers' license records (those < 65 years of age) and Medicare enrollment files (those > or = 65 years of age). Between 1994 and 1997, a total of 540 controls were interviewed and toenail samples of sufficient weight were collected from 506 (93.7%) of these. Beginning in 1995, a sample of tap water was taken from the participants' homes; a total of 217 (98.6%) water samples were obtained from the 220 subjects interviewed. Arsenic determinations were made from toenail samples using neutron activation analysis. Water samples were analyzed using hydride-generation magnet sector inductively coupled mass spectrometry. Among 208 subjects with both toenail and water measurements, the correlation (r) between water and nail arsenic was 0.65 (p < 0.001) among those with water arsenic concentrations of 1 microg/liter or higher and 0.08 (p = 0.31) among those with concentrations below 1 microg/liter (overall r = 0.46, p < 0.001). Our data suggest that toenail samples provide a useful biologic marker for quantifying low-level arsenic exposure.

Adult↗

PubMed2000

Chromosome translocations in breast cancer with breakpoints at 8p12.

Unbalanced chromosome translocations with breakpoints around 8p12, resulting in loss of distal 8p, are common in carcinomas. We have mapped the 8p12 breakpoints in three breast cancer cell lines, T-47D, MDA-MB-361, and ZR-75-1, using YACs and PACs between D8S540 and D8S255 by fluorescence in situ hybridization. All three lines had a breakpoint close to D8S505, proximal to HGL. Each breakpoint was distinct, but all were within 0.5 to 1.5 Mb of each other. The T-47D cell line had a straightforward translocation, but in MDA-MB-361 and ZR-75-1 the translocations were accompanied by local rearrangements of surprising complexity. Small regions of 8p from close to the breakpoint were duplicated or amplified as inserts in the attached chromosome fragment. ZR-75-1 also had retained a separate fragment of about 1 Mb, from the region 1 to 3 Mb telomeric to the common breakpoint, that included HGL. This line also had an interstitial deletion several megabases more centromeric. The data suggest that breakpoints on 8p12 are clustered in a small region and show that translocations breaking there may be accompanied by additional rearrangements.

Bacteriophages↗

PubMed2000

Differential role of tyrosine phosphorylation in adhesion-induced transcription, mRNA stability, and cytoskeletal organization in human monocytes.

Monocyte adhesion resulted in rapid tyrosine phosphorylation and subsequent cytokine mRNA induction. The objective of this study was to determine the role of specific tyrosine phosphorylation events, particularly those involving members of the MAP kinase family, in regulating adhesion-induced cytokine expression. Using nuclear run-on analyses, we demonstrated that on adhesion, monocytes rapidly transcriptionally activated numerous cytokine mRNAs, coincident with the activation of the transcription factors NF-KB and AP-1. Both an inhibitor of tyrosine phosphorylation, genistein, and the cytoplasmic tyrosine phosphatase PTP1B, were unable to prevent adhesion-mediated transcriptional activation. However, both blocked adhesion-induced ERK and JNK but not p38 kinase activation and at the same time decreased the stability of interleukin-1beta (IL-1beta) and IL-8 transcripts. In addition, whereas adhesive events occurred in the presence of genistein and PTP1B, monocyte spreading was markedly inhibited. Our results suggest that the majority of protein phosphorylation events are associated with adhesion-induced cytokine expression through transcript stabilization and cytoskeletal organization. A minority of protein phosphorylation events, not sensitive to genistein or PTP1B exposure, may be instrumental in regulating transcription. Thus the spectrum of protein tyrosine kinases required for transcription appear distinct from those involved in maintaining the stability of some cytokine mRNAs and the integrity of the cytoskeleton to which mRNA destined for translation must be associated.

Adult↗

PubMed2000

Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density.

To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.

Absorptiometry, Photon↗

PubMed2000

Evaluation of 24-color multifluor-fluorescence in-situ hybridization (M-FISH) karyotyping by comparison with reverse chromosome painting of the human breast cancer cell line T-47D.

Multifluor-fluorescence in-situ hybridization (M-FISH) chromosome paints for all the chromosomes in the human complement labeled with different combinations of fluorochromes is a recent technological development enabling assignment of chromosomal material to rearranged chromosomes. Little data is available on the accuracy and limitations of the approach to the analysis of complex karyotypes, which are characteristic of many malignant diseases. Here we compare M-FISH analysis of the breast-cancer-derived cell line T-47D with a previous analysis by reverse chromosome painting analysis of flow-sorted chromosomes from the same material. This demonstrated a high degree of concordance. It also illustrated the limitations of M-FISH analysis, including difficulties identifying small regions of chromosomal material and intrachromosomal rearrangements. Confirmation of selected aberrations using less-complex mixtures of painting probes and further definition of abnormalities using single copy markers may be required. The detailed karyotype description possible by M-FISH analysis contrasts with the definition in the original G-banding analysis. This and the level of concordance with reverse FISH painting supports the utility of the approach in the definition of complex karyotypes.

Breast Neoplasms↗

PubMed2000

Effects of selenium deficiency on tissue selenium content, deiodinase activity, and thyroid hormone economy in the rat during development.

The iodothyronine deiodinases, D1, D2, and D3, all contain selenium (Se) in the form of selenocysteine at their active sites, and they play crucial roles in determining the circulating and intracellular levels of the active thyroid hormone (TH), T3. However, not only are serum T3 levels normal in Se-deficient rats but phenotypic and reproductive abnormalities are minimal, and it has been suggested that regulatory mechanisms exist to conserve Se in critical tissues. The present study was designed to determine, in rats: 1) whether the effects of Se-deficiency are greater in the fetus and neonate than in the adult; 2) whether there are tissues other than brain and thyroid in which deiodinase activities are maintained; 3) whether the maintenance of deiodinase activity in a specific tissue is associated with a concomitant preservation of Se level in that tissue; and 4) whether TH economy and general health is maintained over several generations. The tissues studied included liver, cerebrum, thyroid, pituitary, skin, brown adipose tissue, uterus, ovary, testis, placenta, and the implantation site (uterus plus contents) at E9. The results have revealed that, with the exception of liver, skin, and nonpregnant uterus, all of the tissues studied maintained substantial deiodinase activity (>50%) during prolonged Se-deficiency. Second, although the ability of a tissue to maintain deiodinase activity in the face of dietary Se deprivation was associated in some tissues with a concomitant local preservation of Se concentration, this was not the case for all tissues. Only when Se levels were decreased by more than 80% was deiodinase activity markedly decreased. Third, the effects of Se-deficiency were no greater in the fetus than in the adult; and fourth, at the level of Se-deficiency employed in this study, TH economy and general health were successfully maintained over six generations of Se-deficient rats. How Se levels are maintained in specific tissues, whether Se is sequestered in specific cells of a tissue or organ during dietary Se deprivation, and the precise mechanisms by which plasma T3 levels are maintained in Se-deficient animals remain unanswered. Further insights may be gained by using diets that are even lower in Se than those that were used herein and/or by conducting studies using radioactive forms of Se and thyroid hormones.

Aging↗

PubMed2000

Morphodensitometric analysis of protein kinase C beta(II) expression in rat colon: modulation by diet and relation to in situ cell proliferation and apoptosis.

We have recently demonstrated that overexpression of PKC beta(II) renders transgenic mice more susceptible to carcinogen-induced colonic hyperproliferation and aberrant crypt foci formation. In order to further investigate the ability of PKC beta(II) to modulate colonocyte cytokinetics, we determined the localization of PKC beta(II) with respect to cell proliferation and apoptosis along the entire colonic crypt axis following carcinogen and diet manipulation. Rats were provided diets containing either corn oil [containing n-6 polyunsaturated fatty acids (PUFA)] or fish oil (containing n-3 PUFA), cellulose (non-fermentable fiber) or pectin (fermentable fiber) and injected with azoxymethane (AOM) or saline. After 16 weeks, an intermediate time point when no macroscopic tumors are detected, colonic sections were utilized for immunohistochemical image analysis and immunoblotting. Cell proliferation was measured by incorporation of bromodeoxyuridine into DNA and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling. In the distal colon, PKC beta(II) staining was localized to the upper portion of the crypt. In comparison, proximal crypts had more (P < 0.05) staining in the lower tertile. AOM enhanced (P < 0.05) PKC beta(II) expression in all regions of the distal colonic crypt (upper, middle and lower tertiles). There was also an interaction (P < 0.05) between dietary fat and fiber on PKC beta(II) expression (corn/pectin > fish/cellulose, fish/pectin > corn/cellulose) in all regions of the distal colonic crypt. With respect to colonic cell kinetics, proliferation paralleled the increase in PKC beta(II) expression in carcinogen-treated animals. In contrast, apoptosis at the lumenal surface was inversely proportional to PKC beta(II) expression in the upper tertile. These results suggest that an elevation in PKC beta(II) expression along the crypt axis in the distal colon is linked to enhancement of cell proliferation and suppression of apoptosis, predictive intermediate biomarkers of tumor development. Therefore, select dietary factors may confer protection against colon carcinogenesis in part by blocking carcinogen-induced PKC beta(II) expression.

Animals↗

PubMed2000

Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation.

There is epidemiological, clinical, and experimental evidence that dietary fish oil, containing n-3 polyunsaturated fatty acids, protects against colon tumor development. However, its effects on colonocytes in vivo remain poorly understood. Therefore, we investigated the ability of fish oil to modulate colonic methylation-induced DNA damage, repair, and deletion. Sprague Dawley rats were provided with complete diets containing either corn oil or fish oil (15% by weight). Animals were injected with azoxymethane, and the distal colon was removed 3, 6, 9, or 12 h later. Targeted apoptosis and DNA damage were assessed by cell position within the crypt using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay and quantitative immunohistochemical analysis of O6-methylguanine adducts, respectively. Localization and expression of the alkyl group acceptor, O6-methylguanine-DNA-methyltransferase, was also determined. Lower levels of adducts were detected at 6, 9, and 12 h in fish oil- versus corn oil-fed animals (P < 0.05). In addition, fish oil supplementation had the greatest effect on apoptosis in the top one-third of the crypt, increasing the apoptotic index compared with corn oil-fed rats (P < 0.05). In the top one-third of the crypt, fish oil feeding caused an incremental stimulation of apoptosis as adduct level increased. In contrast, a negative correlation between apoptosis and adduct incidence occurred with corn oil feeding (P < 0.05). Diet had no main effect (all tertiles combined) on O6-methylguanine-DNA-methyltransferase expression over the time frame of the experiment. The enhancement of targeted apoptosis combined with the reduced formation of O6-methylguanine adducts may account, in part, for the observed protective effect of n-3 polyunsaturated fatty acids against experimentally induced colon cancer.

Analysis of Variance↗

PubMed1999

A subcortical pathway to the right amygdala mediating "unseen" fear.

Neuroimaging studies have shown differential amygdala responses to masked ("unseen") emotional stimuli. How visual signals related to such unseen stimuli access the amygdala is unknown. A possible pathway, involving the superior colliculus and pulvinar, is suggested by observations of patients with striate cortex lesions who show preserved abilities to localize and discriminate visual stimuli that are not consciously perceived ("blindsight"). We used measures of right amygdala neural activity acquired from volunteer subjects viewing masked fear-conditioned faces to determine whether a colliculo-pulvinar pathway was engaged during processing of these unseen target stimuli. Increased connectivity between right amygdala, pulvinar, and superior colliculus was evident when fear-conditioned faces were unseen rather than seen. Right amygdala connectivity with fusiform and orbitofrontal cortices decreased in the same condition. By contrast, the left amygdala, whose activity did not discriminate seen and unseen fear-conditioned targets, showed no masking-dependent changes in connectivity with superior colliculus or pulvinar. These results suggest that a subcortical pathway to the right amygdala, via midbrain and thalamus, provides a route for processing behaviorally relevant unseen visual events in parallel to a cortical route necessary for conscious identification.

Adult↗

PubMed1999

Covariation of activity in habenula and dorsal raphé nuclei following tryptophan depletion.

Abnormal serotonergic function is implicated in the pathogenesis of affective disorders. We induced transient depressive relapses in volunteer patients by rapidly depleting plasma tryptophan, the precursor of serotonin (5-HT), and measured neural activity during different cognitive tasks using positron emission tomography (PET). Neural activity in several 5-HT-related brain areas, e.g., dorsal raphé, habenula, septal region, amygdala, and orbitofrontal cortex, covaried significantly with plasma levels of tryptophan and ratings of depressed mood. Task-specific responses in left amygdala and left anterior cingulate were attenuated by tryptophan depletion. We used these PET data to test the hypothesis that projections from the habenula modulate dorsal raphé activity and that this modulation is enhanced in patients experiencing a profound mood change following serotonergic challenge. A strong linear correlation (r(2) > 0.5) between habenula and raphé activity was observed in subjects with postdepletion ratings >/=10 on a modified Hamilton depression scale, whereas subjects experiencing milder changes in mood had weaker habenula-raphé coupling (r(2) < 0.5). These data support a model of the serotonergic system in which the habenula projection to the raphé represents a convergent feedback pathway that controls the release of 5-HT throughout the brain. In our experiment we were able to engage this system in patients who were sensitive to tryptophan depletion.

Adult↗

PubMed1999

Saying it with feeling: neural responses to emotional vocalizations.

To determine how vocally expressed emotion is processed in the brain, we measured neural activity in healthy volunteers listening to fearful, sad, happy and neutral non-verbal vocalizations. Enhanced responses to emotional vocalizations were seen in the caudate nucleus, as well as anterior insular, temporal and prefrontal cortices. The right amygdala exhibited decreased responses to fearful vocalizations as well as fear-specific inhibitory interactions with left anterior insula. A region of the pons, implicated in acoustic startle responses also showed fear-specific interactions with the amygdala. The data demonstrate: firstly, that processing of vocal emotion involves a bilaterally distributed network of brain regions; and secondly, that processing of fear-related auditory stimuli involves context-specific interactions between the amygdala and other cortical and brainstem regions implicated in fear processing.

Adult↗

PubMed1999

Dissociable neural responses to facial expressions of sadness and anger.

Previous neuroimaging and neuropsychological studies have investigated the neural substrates which mediate responses to fearful, disgusted and happy expressions. No previous studies have investigated the neural substrates which mediate responses to sad and angry expressions. Using functional neuroimaging, we tested two hypotheses. First, we tested whether the amygdala has a neural response to sad and/or angry facial expressions. Secondly, we tested whether the orbitofrontal cortex has a specific neural response to angry facial expressions. Volunteer subjects were scanned, using PET, while they performed a sex discrimination task involving static grey-scale images of faces expressing varying degrees of sadness and anger. We found that increasing intensity of sad facial expression was associated with enhanced activity in the left amygdala and right temporal pole. In addition, we found that increasing intensity of angry facial expression was associated with enhanced activity in the orbitofrontal and anterior cingulate cortex. We found no support for the suggestion that angry expressions generate a signal in the amygdala. The results provide evidence for dissociable, but interlocking, systems for the processing of distinct categories of negative facial expression.

Adult↗

PubMed1999

Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion.

BACKGROUND: Acute tryptophan depletion lowers brain serotonin synthesis and results in a transient, but striking, clinical relapse in recovered depressed patients. AIMS: To identify brain regions which change their activity as an acute depressive relapse evolves and to determine how pathological mood might modulate neural activity during a cognitive task. METHOD: We used H2(15)O positron-emission tomography (PET) to study eight recovered depressed men after tryptophan depletion and after a control procedure. During both PET scan sessions, subjects performed a paced verbal fluency task which alternated with a control verbal repetition task. RESULTS: Increasing levels of depression after tryptophan depletion were associated with diminished neural activity in the ventral anterior cingulate, orbitofrontal cortex and caudate nucleus regions. In addition, depressive relapse attenuated cognitive task-related activation in the anterior cingulate cortex. CONCLUSIONS: Our data indicate that changes in neural activity in distinct brain regions mediate the clinical phenomena of depression and depression-related cognitive impairment following acute tryptophan depletion. These changes could be associated with the widespread distribution of serotonin neurons in brain pathways associated with the expression of affect and cognitive performance.

Adult↗

PubMed1999

Relationship between DNA adduct levels, repair enzyme, and apoptosis as a function of DNA methylation by azoxymethane.

DNA alkylating agent exposure results in the formation of a number of DNA adducts, with O6-methyl-deoxyguanosine (O6-medG) being the major mutagenic and cytotoxic DNA lesion. Critical to the prevention of colon cancer is the removal of O6-medG DNA adducts, either through repair, for example, by O6-alkylguanine-DNA alkyltransferase (ATase) or targeted apoptosis. We report how rat colonocytes respond to administration of azoxymethane (a well-characterized experimental colon carcinogen and DNA-methylating agent) in terms of O6-medG DNA adduct formation and adduct removal by ATase and apoptosis. Our results are: (a) DNA damage is greater in actively proliferating cells than in the differentiated cell compartment; (b) expression of the DNA repair enzyme ATase was not targeted to the proliferating cells or stem cells but rather is confined primarily to the upper portion of the crypt; (c) apoptosis is primarily targeted to the stem cell and proliferative compartments; and (d) the increase in DNA repair enzyme expression over time in the bottom one-third of the crypt corresponds with the decrease in apoptosis in this same crypt region.

Alkyl and Aryl Transferases↗