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Modern treatment strategies in polycythemia vera.

Polycythemia vera (PV), one of the chronic myeloproliferative disorders (MPD), is characterized by predominant erythroid proliferation and secondary platelet proliferation, and by progression from a proliferative stage to a metastatic phase and finally a malignant phase. These characteristics expose patients to increased risk for thrombohemorrhagic complications, myeloid metaplasia, myelofibrosis, and acute leukemic conversion irrespective of treatments. Currently, there are three agents-hydroxyurea (HU), interferon-alfa (IFN-alpha), and anagrelide-that differ in mechanisms of action and in treating specific phenotypic manifestations of PV, suggesting a potential role for combination therapy. They also differ widely in side effects profiles and severity. Because of the differing risks for long-term complications associated with these agents, age is an important variable in selecting treatments. Patients at high risk for thrombohemorrhagic complications all require cytoreduction, as do patients at intermediate risk who are not effectively managed by phlebotomy and low-dose aspirin. In younger patients, the safest and most effective combination treatment appears to be anagrelide plus IFN-alpha, while in older patients anagrelide plus hydroxyurea may be effective. HU is used sparingly in younger patients because of the long-term increased risk of mutagenicity and possibly leukemogenesis. IFN-alpha is particularly indicated for patients with myeloid metaplasia evidenced by splenomegaly. Anagrelide, which acts on the mature megakaryocyte to prevent platelet budding, is uniquely efficacious in the control of platelet counts.

Age Factors↗

Relationship between DNA ploidy level, nuclear size, and survival in large cell lymphoma.

Intermediate and high grade subtypes of non-Hodgkin's large cell (LCL) and immunoblastic lymphomas exhibit considerable variability, and histologic morphology alone may not adequately characterize those features important for prognosis. The relationship between nuclear morphology and survival was assessed in a series of 50 cases of large cell lymphomas in which ploidy, proliferation, and nuclear area (NA) were measured. Ploidy was calculated by both DNA index (DI) and DNA histogram type (DHT). Proliferation was calculated from the proportion of S phase (SPF) cells present in the DHT. These four parameters were measured using image cytometry of Feulgen-stained nuclei from fine-needle aspirations. To characterize the relationship with survival, these parameters were associated with the clinical follow-up of the patients. The results show that of the 50 LCL cases, only 5 were clearly aneuploid, whereas the remaining 45 were either diploid (29 cases), tetraploid/hypotetraploid (13 cases), or weakly aneuploid (hyperdiploid, 3 cases). Of the 34 patients who died from their disease, both smaller NA and DI correlated with longer survival in an equivalent fashion; neither conferred greater sensitivity when combined with the other. The SPF did not correlate with survival. In LCL, aneuploidy seems to be a relatively uncommon event, but when present ploidy measurement appears useful to define prognosis.

Adult↗

Percutaneous or surgical tracheostomy: a meta-analysis.

OBJECTIVE: To compare percutaneous with surgical tracheostomy using a meta-analysis of studies published from 1960 to 1996. DATA SOURCES: Publications obtained through a MEDLINE database search with a Boolean combination (tracheostomy or tracheotomy) and complications, with constraints for human studies and English language. STUDY SELECTION: Publications addressing all peri- and postoperative complications. Studies limited to specific tracheostomy complications or containing insufficient details were excluded. Two authors independently selected the publications. DATA EXTRACTION: A list of relevant surgical variables and complications was compiled. Complications were divided into peri- and postoperative groups and further subclassified into severe, intermediate, and minor groups. Because most studies of percutaneous tracheostomy were published after 1985, surgical tracheostomy studies were divided into two periods: 1960 to 1984 and 1985 to 1996. The articles were analyzed independently by three investigators, and rare discrepancies were resolved through discussion and data reexamination. DATA SYNTHESIS: Earlier surgical tracheostomy studies (n = 17; patients, 4185) have the highest rates of both peri- (8.5%) and postoperative (33%) complications. Comparison of recent surgical (n = 21; patients, 3512) and percutaneous (n = 27; patients, 1817) tracheostomy trials shows that perioperative complications are more frequent with the percutaneous technique (10% vs. 3%), whereas postoperative complications occur more often with surgical tracheotomy (10% vs. 7%). The bulk of the differences is in minor complications, except perioperative death (0.44% vs. 0.03%) and serious cardiorespiratory events (0.33% vs. 0.06%), which were higher with the percutaneous technique. Heterogeneity analysis of complication rates shows higher heterogeneity in older and surgical trials. CONCLUSIONS: Percutaneous tracheostomy is associated with a higher prevalence of perioperative complications and, especially, perioperative deaths and cardiorespiratory arrests. Postoperative complication rates are higher with surgical tracheostomy.

Adult↗

Crassulacean Acid Metabolism and Crassulacean Acid Metabolism Modifications in Peperomia camptotricha.

Peperomia camptotricha, a tropical epiphyte from Mexico, shows variable forms of Crassulacean acid metabolism (CAM). Young leaves exhibit CAM-cycling, while mature leaves show an intermediate type of metabolism, between CAM and CAM-cycling, having approximately the same amount of nighttime gas exchange as daytime. Metabolism of young leaves appears independent of daylength, but mature leaves have a tendency toward more CAM-like metabolism under short days (8 hours). Large differences in the physical appearance of plants were found between those grown under short daylengths and those grown under long daylengths (14 hours). Some anatomical differences were also detected in the leaves. Water stress caused a switch to CAM in young and mature leaves, and as water stress increased, they shifted to CAM-idling.

Journal Article↗

Polymorphisms of the upstream regulatory region of the major histocompatibility complex DRB genes in domestic horses.

Sequence information was obtained on the variation of the ELA-DRB upstream regulatory region (URR) after polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) cloning and sequencing of approximately 220 bp upstream of the first exon of horse DRB genes. The sequence of the proximal URR of equine DRB is composed of highly conserved sequence motifs, showing the presence of the W, X, Y, CAAT and TATA conserved boxes of major histocompatibility complex (MHC) class II promoters. Five different polymorphic horse DRB promoter sequences were detected in five horse breeds. The results demonstrate the existence of polymorphism in the nucleotide sequences of the ELA-DRB URR, located in the functionally important conserved consensus sequences, the X2 box, the Y box and the TATA box, while conservation were observed in X1 and CAAT boxes. The nucleotide diversity among horse URRs was intermediate between that seen within human and mouse DRB promoters, suggesting the existence of another important source of variability in ELA-DRB genes. In addition, phylogenetic comparisons, identity analysis and sequence organization suggested that the reported sequences would correspond to an expressed ELA-DRB locus. However, further information about the functional significance of these promoter polymorphisms will probably be acquired through expression studies on the different sequences.

Animals↗

Sulphorhodamine-labelled cells in the neonatal rat spinal cord following chemically induced locomotor activity in vitro.

1. Sulphorhodamine 101, a fluorescent dye and newly identified activity marker, was used to localize potential spinal locomotor networks in the neonatal rat spinal cord. 2. Preparations of the spinal cord with one entire hindlimb attached or the spinal cord in isolation were kept in vitro. Spinal locomotor activity was maintained chemically with NMDA (5-7.5 microM), in combination with 5-HT (7.5-20 microM), for 4-4.5 h in the presence of 0.0001-0.0005% sulphorhodamine 101. Matched non-locomoting controls were exposed to the dye in the absence of transmitters for a comparable time. Transverse sections of the lumbar spinal cord (L1-L6) were screened for rhodamine emission using an epifluorescence microscope. 3. In hindlimb-attached locomoting preparations with intact dorsal roots, labelled cells were found on the leg side in the dorsal horn (mainly laminae II-IV), in the intermediate grey (lamina VI-VII) and around the central canal (lamina X). Dorsal rhizotomy was performed on the leg side, to prevent synaptic activity due to afferent inflow. This largely reduced the number of labelled cells in the dorsal horn and in the lateral part of the intermediate grey matter. A further reduction of labelling in these areas was seen after complete isolation of the cord or when compared to the legless side, with the majority of labelled cells persisting in a bilateral cluster close to the central canal and in the medial intermediate grey. Few labelled cells were observed in non-locomoting preparations. The intensity of motoneuronal labelling was variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An inherently stable boundary-condition-transfer algorithm for muffler analysis.

Wave coupling exists in the wave propagation in multiple interacting ducts within a waveguide. One may use the segmentation approach, decoupling approach, eigenvalue approach, or the matrizant approach to derive the overall transfer matrix for the muffler section with interacting ducts, and then apply the terminal boundary conditions to obtain a two-by-two transfer matrix. In such instances, a boundary condition applied to a vector is given as a linear combination of its components. Spatial dimensions along with parameters like impedance of the perforated interface may yield numerical instability during computation leading to inaccurate prediction of the acoustic performance of mufflers. Here, an inherently stable boundary-condition-transfer approach is discussed to analyze the plane wave propagation in suchlike mufflers and applied to waveguides of variable cross-sectional area. The concept of pseudo boundary conditions applied to the state vector at an intermediate point is outlined. The method is checked for self-consistency and shown to be stable even for extreme geometries.

Journal Article↗

Anaerobic degradation of phthalate isomers by methanogenic consortia.

Three methanogenic enrichment cultures, grown on ortho-phthalate, iso-phthalate, or terephthalate were obtained from digested sewage sludge or methanogenic granular sludge. Cultures grown on one of the phthalate isomers were not capable of degrading the other phthalate isomers. All three cultures had the ability to degrade benzoate. Maximum specific growth rates (microseconds max) and biomass yields (YXtotS) of the mixed cultures were determined by using both the phthalate isomers and benzoate as substrates. Comparable values for these parameters were found for all three cultures. Values for microseconds max and YXtotS were higher for growth on benzoate compared to the phthalate isomers. Based on measured and estimated values for the microbial yield of the methanogens in the mixed culture, specific yields for the phthalate and benzoate fermenting organisms were calculated. A kinetic model, involving three microbial species, was developed to predict intermediate acetate and hydrogen accumulation and the final production of methane. Values for the ratio of the concentrations of methanogenic organisms, versus the phthalate isomer and benzoate fermenting organisms, and apparent half-saturation constants (KS) for the methanogens were calculated. By using this combination of measured and estimated parameter values, a reasonable description of intermediate accumulation and methane formation was obtained, with the initial concentration of phthalate fermenting organisms being the only variable. The energetic efficiency for growth of the fermenting organisms on the phthalate isomers was calculated to be significantly smaller than for growth on benzoate.

Acetates↗

Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection.

To understand the high variability of the asymptomatic interval between primary human immunodeficiency virus type 1 (HIV-1) infection and the development of AIDS, we studied the evolution of the C2-V5 region of the HIV-1 env gene and of T-cell subsets in nine men with a moderate or slow rate of disease progression. They were monitored from the time of seroconversion for a period of 6 to 12 years until the development of advanced disease in seven men. Based on the analysis of viral divergence from the founder strain, viral population diversity within sequential time points, and the outgrowth of viruses capable of utilizing the CXCR4 receptor (X4 viruses), the existence of three distinct phases within the asymptomatic interval is suggested: an early phase of variable duration during which linear increases ( approximately 1% per year) in both divergence and diversity were observed; an intermediate phase lasting an average of 1.8 years, characterized by a continued increase in divergence but with stabilization or decline in diversity; and a late phase characterized by a slowdown or stabilization of divergence and continued stability or decline in diversity. X4 variants emerged around the time of the early- to intermediate-phase transition and then achieved peak representation and began a decline around the transition between the intermediate and late phases. The late-phase transition was also associated with failure of T-cell homeostasis (defined by a downward inflection in CD3(+) T cells) and decline of CD4(+) T cells to </=200 cells/microliter. The strength of these temporal associations between viral divergence and diversity, viral coreceptor specificity, and T-cell homeostasis and subset composition supports the concept that the phases described represent a consistent pattern of viral evolution during the course of HIV-1 infection in moderate progressors. Recognition of this pattern may help explain previous conflicting data on the relationship between viral evolution and disease progression and may provide a useful framework for evaluating immune damage and recovery in untreated and treated HIV-1 infections.

Base Sequence↗

Exercise training enhances adrenergic constriction and dilation in the rat spinotrapezius muscle.

Treadmill training increases functional vasodilation in the rat spinotrapezius muscle, although there is no acute increase in blood flow and no increase in oxidative capacity. To assess concurrent changes in vascular reactivity, we measured arterial diameters in the spinotrapezius muscle of sedentary (Sed) and treadmill-trained (Tr; 9-10 wk; terminal intensity 30 m/min, 1.5 degrees incline, for 90 min) rats during iontophoretic application of norepinephrine, epinephrine (Epi), and H+ (HCl) and during superfusion with adenosine. Terminal-feed arteries and first-order arterioles in Tr rats constricted more than those in Sed rats at the higher current doses of norepinephrine and Epi. In contrast, at low-current doses of Epi, first- and second-order arterioles dilated in Tr but not in Sed rats. The vascular responses to HCl were highly variable, but second-order arterioles of Tr rats constricted more than those of Sed rats at intermediate-current doses. There were no significant differences between Sed and Tr rats in the vascular responses to adenosine. Both adrenergic vasodilation and vasoconstriction were enhanced in the spinotrapezius muscle of Tr rats, and enhanced adrenergic vasodilation may contribute to increased functional vasodilation. These observations further demonstrate vascular adaptations in "nontrained" skeletal muscle tissues.

Adenosine↗

Physiological properties of muscle spindles in dorsal neck muscles of the cat.

1. Single-fiber recording was used to examine the properties of 107 spindle endings in cat biventer cervicis (BC) and complexus (CM) muscles. Responses of receptors were examined following muscle contraction and ramp and hold stretch. Twenty-two endings in splenius (SP) were also examined, but their responses could not be quantitated because the anatomy of SP prevented the application of appropriate stretches. 2. Conduction velocitites of spindle afferents ranged from 13 to 90 m/s. Endings with primary response patterns usually had faster conduction velocities than secondary endings, but there was overlap in the conduction velocity ranges of the two subgroups. 3. Most neck spindle afferents could be classified as either primary or secondary by a constellation of physiological criteria including dynamic response pattern, dynamic index, and variability of resting discharge frequency. However, 22 of 107 endings from BC and CM had responses with characteristics intermediate between primary and secondary responses. The possible sources of these characteristics are discussed. 4. Despite the similarity in properties between spindles of different neck muscles, the length sensitivities of CM spindles were high compared to those of BC spindles. CM spindles showed length-related modulation of firing frequency over a more restricted range of initial muscle lengths than did BC spindles. 5. Eight Golgi tendon organs (GTO) were identified by their characteristics responses. Conduction velocities obtained for five GTO afferent nerves ranged from 50 to 67 m/s. Recordings were also made from receptros in deep muscles surrounding the vertebrae. These receptors had properties characteristic of muscle spindles.

Adaptation, Physiological↗

Splenic marginal zone lymphoma: a prognostic model for clinical use.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100,000/microL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

Adult↗

Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group.

PURPOSE: To investigate whether primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathologic entity with a more aggressive course than other diffuse large B-cell lymphomas (DLBL). MATERIALS AND METHODS: All patients with CD20-positive DLBL who presented with a mediastinal mass measuring at least 5.0 cm and were treated with curative intent were identified. A control group of 352 patients with nonmediastinal DLBL was selected for comparison. RESULTS: The 43 patients with PMLBL had a male to female ratio of 20:23 and a median age of 42 years. Stage I/II disease was present in 58% of the patients, with only 9% having bone marrow involvement. A complete remission was achieved in 63% of the patients, and the 5-year overall and failure-free survivals were 46% and 38%, respectively. Among the clinical variables, an elevated serum lactate dehydrogenase level, a low performance score, more than one extranodal site, and an intermediate or high International Prognostic Index score were predictive of poor survival. When compared with the DLBL group, a younger median age was the only clinical feature that was significantly different in the PMLBL group. CONCLUSION: The clinical features of PMLBL do not appear to be significantly different from those of nonmediastinal DLBL. Although the younger age of onset, slight female predominance, mediastinal location, and size of the mass may justify the recognition of PMLBL as a clinical syndrome, additional evidence is needed to define it as a distinct disease entity.

Adolescent↗

The relationship between placental and other perinatal risk factors for neurologic impairment in very low birth weight children.

Placental abnormalities reflect antenatal disease processes that may interact with other perinatal risk factors to affect long-term outcome. We performed a nested case control analysis of placental and clinical risk factors associated with neurologic impairment (NI) at 20-mo corrected age (60 cases and 59 controls) using data collected in a prospective study of very low birth weight (less than 1500 g) infants born between 1983 and 1991. In a preliminary analysis we explored the relationship between clinical infection and histologic chorioamnionitis (CA). Only histologic CA with a fetal vascular response correlated with either clinical CA or early onset neonatal sepsis. We then assessed the relative contribution of the nine risk factors (four placental and five clinical) associated with NI at the univariate level by multiple logistic regression. Three risk factors were independent predictors of NI: severe cranial ultrasound abnormalities (odds ratio 13.6, 95% confidence intervals 4.5-66.7), multiple placental lesions (odds ratio 13.2, 95% confidence intervals 1.3-137.0), and oxygen dependence at 36 wk (odds ratio 4.2, 95% confidence intervals 1.2-14.6). Finally, a series of logistic regressions was conducted with the dependent variable changing as we moved back along the causal chain to explore the relationships between risk factors operating at different stages. This analysis suggested that antenatal variables that were not independent predictors of NI by multiple logistic regression exerted their effects through the following intermediate pathways: fetal grade 3 histologic CA via chorionic vessel thrombi, clinical CA via grade 3 villous edema, and grade 3 villous edema via severe cranial ultrasound abnormalities.

Case-Control Studies↗

Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt.

We consider some of the problems involved in current discussions on stem cells in adult mammalian tissues. The present concepts involve a number of pitfalls, weaknesses and logical, semantic and classification problems. This indicates the necessity for new and well-defined concepts that are amenable to experimental analysis. One of the major difficulties in considering stem cells is that they are defined in terms of their functional capabilities which can only be assessed by testing the abilities of the cells, which itself may alter their characteristics during the assay procedure: a situation similar to the uncertainty principle in physics. The terms that describe stem cell functions are often not well defined and are used loosely, which can lead to confusion. If such context-dependent interactions exist between the manipulation and measurement process and the challenged stem cells, the question of, for example, the number of stem cells, in a tissue has to be posed in a new way. Rather than obtaining a single number one might end up with various different numbers under different circumstances, all being complementary. This might suggest that stemness is not a property but a spectrum of capabilities from which to choose. This concept might facilitate a reconciliation between the different and sometimes opposing experimental results. Given certain experimental evidence, we have attempted to provide a novel concept to describe structured cell populations in tissues involving stem cells, transit cells and mature cells. It is based on the primary assumption that the proliferation and differentiation/maturation processes are in principle independent entities in the sense that each may proceed without necessarily affecting the other. Stem cells may divide without maturation while cells approaching functional competence may mature but do not divide. In contrast, transit cells divide and mature showing intermediate properties between stem cells and mature functional cells. The need to describe this transition process and the variable coupling between proliferation and maturation leads us to formulate a spiral model of cell and tissue organisation. This concept is illustrated for the intestinal epithelium. It is concluded that the small intestinal crypts contain 4-16 actual stem cells in steady state but up to 30-40 potential stem cells (clonogenic cells) which may take over stem cell properties following perturbations. This implies that transit cells can under certain circumstances behave like actual stem cells while they undergo maturation under other conditions. There is also evidence that the proliferation and differentiation/maturation processes are subject to controls that ultimately lead to a change in the spiral trajectories.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Spatial patterns of labile forms of phosphorus in a subtropical wetland.

Phosphorus (P) has been identified as the key constituent defining wetland productivity, structure, and function. Our goal was to investigate the spatial patterns of total P and three labile forms of P (labile organic, inorganic, and microbial biomass P) across a subtropical wetland located in east-central Florida, the Blue Cypress Marsh Conservation Area (BCMCA), and link spatial patterns to ecosystem processes. The wetland received a continual input of nutrients primarily from the south and intermittently from the west and east, respectively, which ceased in the mid-1990s. Since then the marsh system has been undergoing natural succession. We used (i) ordinary kriging to characterize the spatial patterns of total P and labile P forms across the wetland, (ii) local, moving spatial correlations to investigate relationships between total P and labile P forms, and (iii) a clustering technique to link the identified spatial patterns to biogeochemical processes. The spatially explicit analyses revealed patterns of total P and labile P forms as well as changing relationships between variables across the marsh. We were able to distinguish P-enriched areas from unaffected ("natural") areas and intermediate zones that are currently undergoing change as P is mobilized and translocated. We also identified areas that are at risk, showing a shift toward a more P-enriched status. Our results improve our understanding of P and its labile components within a spatially explicit context.

Ecosystem↗

Light microscopic detection of BCR-ABL transcripts after in-cell RT-PCR: fusion gene expression might correlate with clinical evolution of chronic myeloid leukemia.

A procedure for in-cell amplification of the hybrid BCR-ABL mRNA by reverse transcription and polymerase chain reaction (RT-PCR) without extraction of the nucleic acids was performed directly in fixed and permeabilized cells of leukemia patients (22 patients with Ph'-positive chronic myeloid leukaemia-CML and 1 with Ph'-positive acute leukaemia-AL, as well as 7 Ph'-negative cases) and Ph'-positive human leukaemia cell lines (K562, LAMA-84, BV173). The labelling of the amplified sequences was done employing biotinylated primers and a second PCR in a semi-nested fashion with a low number of cycles. An enzymatic system based on biotin-streptavidin-chromogen reaction was used for the detection of labeled PCR product, thus producing a coloured product, visible to the eye under a standard light microscope. All samples from patients with cytogenetic and molecular evidence of BCR-ABL rearrangement showed specific cytoplasmic staining at the site of the amplified hybrid transcripts. It allowed definite distinction between positive and negative cells. K562, LAMA-84, BV173 cells were characterized with strong diffuse staining while an interesting finding of the present study was the presence of variable quantities of colour product in patients' samples which might be due to different mRNA expression. Early and intermediate stages of myeloid maturation showed more intense reactivity. Cases with an aggressive course of accelerated or blast phase CML and AL were found to have a considerable subset of cells with strongly expressed signal while cases in chronic phase were characterised with uniform weak to moderate reaction. Our observations support the hypothesis that the amount of BCR-ABL transcript expression within neoplastic cells may play a role in dictating the eventual behaviour of the leukaemic clone. Future studies at a single cell level of larger series of consecutive cases with a follow up might be able to identify those patients who are prone to transformation and provide certain indications for further therapeutic decisions.

Adolescent↗

Differences in benzo(a)pyrene metabolism between rodent liver microsomes and embryonic cells.

Differences in benzo(a)pyrene metabolite pattern have been shown by rodent liver microsomes (Sprague-Dawley) and rodent embryo cells from Syrian hamsters and NIH Swiss mice. Rodent liver induced by methylcholanthrene shows marked quantitative variation between species. Additional pattern changes were found in mouse and hamster embryo secondary cultures with a reduction of the K-region metabolites and a marked increase in 9-hydroxybenzo(a)-pyrene. These results are indicative of a region-specific attack on the carcinogen by the cell monooxygenases which is distinct from the liver attack of microsomal enzymes on benzo(a)pyrene. These results suggest that activation and detoxification of benzo(a)pyrene may be species and tissue variable, and susceptibility and resistence to malignant transformation may be predicted on induction of a fortuitous combination of intermediate metabolic steps.

Animals↗