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Biomedical subjects

K Kannan

Publications and source records attributed to K Kannan.

At least 19 recordsLinked to original sources

Polychlorinated dibenzo-p-dioxins, dibenzofurans, and polychlorinated biphenyls in human tissues, meat, fish, and wildlife samples from India.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non- and mono-ortho-substituted polychlorinated biphenyls (dioxin-like PCBs) were measured in tissues of humans, fishes, chicken, lamb, goat, predatory birds, and Ganges River dolphins collected from various locations in India. PCDDs/DFs were found in most of the samples analyzed with the liver of spotted owlet containing the highest concentration of 3,300 pg/g, fat wt. 2,3,7,8-Substituted PCDDs and PCDFs were found in human fattissues at concentrations ranging from 170 to 1,300 pg/g, fat wt. Concentrations of PCDDs were generally greaterthan those of PCDFs in human tissues, fishes, animal fat, and dolphin. Among fishes, meat, and wildlife samples analyzed, concentrations of PCDDs/DFs were found in the following order: country chicken < goat/lamb fat < fishes < river dolphins < predatory birds. Hepta-CDDs and OCDD were the major PCDD homologues found in humans, fishes, meat products, and dolphins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin equivalents of PCDDs/DFs were greater than those of PCBs in selected fish, dolphin, and human samples. To our knowledge, this is the first report of PCDDs and PCDFs in human tissues, fishes, meat, and wildlife collected from India.

Adult↗

Perfluorooctane sulfonate in fish-eating water birds including bald eagles and albatrosses.

Perfluorooctane sulfonate (PFOS) was measured in 161 samples of liver, kidney, blood, or egg yolk from 21 species of fish-eating water birds collected in the United States including albatrosses from Sand Island, Midway Atoll, in the central North Pacific Ocean. Concentrations of PFOS in the blood plasma of bald eagles collected fromthe midwestern United States ranged from 13 to 2,220 ng/mL (mean: 330 ng/mL), except one sample that did not contain quantifiable concentrations of PFOS. Concentrations of PFOS were greater in blood plasma than in whole blood. Among 82 livers from various species of birds from inland or coastal U.S. locations, Brandt's cormorant from San Diego, CA, contained the greatest concentration of PFOS (1,780 ng/g, wet wt). PFOS was also found in the sera of albatrosses from the central North Pacific Ocean at concentrations ranging from 3 to 34 ng/mL. Occurrence of PFOS in birds from remote marine locations suggests widespread distribution of PFOS and related fluorochemicals in the environment.

Animals↗

Multielemental analysis of purpleback flying squad using high resolution inductively coupled plasma-mass spectrometry (HR ICP-MS).

Forty-four elements were analyzed in 21 tissues of purpleback flying squid, Sthenoteuthis oualaniensis, by high resolution inductively coupled plasma-mass spectrometry (HR ICP-MS) and inductively coupled plasma atomic emission spectrophotometry (ICP-AES). Greater concentrations of V, Fe, Co, Ni, Cu, Ag, Cd, Pb, and Bi were found in liver, pancreas, and ink sac than in other tissues. Ink sac concentrated remarkable levels of Ca and Sr in addition to the above-mentioned elements. Several alkalis, alkaline earth, and rare earth elements preferentially accumulated in muscle. Among the hard tissues, accumulation of V and U in beak, Ni, Zn, and Cd in gladius and Cr in skin was prominent. K, Rb, Cs, Pb, Bi and some transition elements (V, Co, Cu, Zn, Ag, Cd) were significantly (p < 0.05) higher in the livers of adult than in juvenile squids. Sodium, alkaline earth, and rare earth elements were higher in the livers of juveniles than in adult squids.

Age Factors↗

DNA microarray analysis of genes involved in p53 mediated apoptosis: activation of Apaf-1.

The transcription regulation activity of p53 controls cellular response to a variety of stress conditions, leading to growth arrest and apoptosis. Despite major progress in the understanding of the global effects of p53 on cellular function the pathways by which p53 activates apoptosis are not well defined. To study genes activated in the p53 induced apoptotic process, we used a mouse myeloid leukemic cell line (LTR6) expressing the temperature-sensitive p53 (val135) that undergoes apoptosis upon shifting the temperature to 32 degrees C. We analysed the gene expression profile at different time points after p53 activation using oligonucleotide microarray capable of detecting approximately 11,000 mRNA species. Cluster analysis of the p53-regulated genes indicate a pattern of early and late induced sets of genes. We show that 91 and 44 genes were substantially up and down regulated, respectively, by p53. Functional classification of these genes reveals that they are involved in many aspects of cell function, in addition to growth arrest and apoptosis. Comparison of p53 regulated gene expression profile in LTR6 cells to that of a human lung cancer cell line (H1299) that undergoes growth arrest but not apoptosis demonstrates that only 15% of the genes are common to both systems. This observation supports the presence of two distinct transcriptional programs in response to p53 signaling, one leading to growth arrest and the other to apoptosis. The proapoptotic genes induced only in LTR6 cells like Apaf-1, Sumo-1 and gelsolin among others may suggest a possible explanation for apoptosis in LTR6 cells.

Apoptosis↗

DNA microarrays identification of primary and secondary target genes regulated by p53.

The transcriptional program regulated by the tumor suppressor p53 was analysed using oligonucleotide microarrays. A human lung cancer cell line that expresses the temperature sensitive murine p53 was utilized to quantitate mRNA levels of various genes at different time points after shifting the temperature to 32 degrees C. Inhibition of protein synthesis by cycloheximide (CHX) was used to distinguish between primary and secondary target genes regulated by p53. In the absence of CHX, 259 and 125 genes were up or down-regulated respectively; only 38 and 24 of these genes were up and down-regulated by p53 also in the presence of CHX and are considered primary targets in this cell line. Cluster analysis of these data using the super paramagnetic clustering (SPC) algorithm demonstrate that the primary genes can be distinguished as a single cluster among a large pool of p53 regulated genes. This procedure identified additional genes that co-cluster with the primary targets and can also be classified as such genes. In addition to cell cycle (e.g. p21, TGF-beta, Cyclin E) and apoptosis (e.g. Fas, Bak, IAP) related genes, the primary targets of p53 include genes involved in many aspects of cell function, including cell adhesion (e.g. Thymosin, Smoothelin), signaling (e.g. H-Ras, Diacylglycerol kinase), transcription (e.g. ATF3, LISCH7), neuronal growth (e.g. Ninjurin, NSCL2) and DNA repair (e.g. BTG2, DDB2). The results suggest that p53 activates concerted opposing signals and exerts its effect through a diverse network of transcriptional changes that collectively alter the cell phenotype in response to stress.

Animals↗

Accumulation of perfluorooctane sulfonate in marine mammals.

Perfluorooctane sulfonate (PFOS) is a perfluorinated molecule that has recently been identified in the sera of nonindustrially exposed humans. In this study, 247 tissue samples from 15 species of marine mammals collected from Florida, California, and Alaskan coastal waters; and northern Baltic Sea; the Arctic (Spitsbergen); and Sable Island in Canada were analyzed for PFOS. PFOS was detected in liver and blood of marine mammals from most locations including those from Arctic waters. The greatest concentrations of PFOS found in liver and blood were 1520 ng/g wet wt in a bottlenose dolphin from Sarasota Bay, FL, and 475 ng/mL in a ringed seal from the northern Baltic Sea (Bothnian Sea), respectively. No age-dependent increase in PFOS concentrations in marine mammals was observed in the samples analyzed. The occurrence of PFOS in marine mammals from the Arctic waters suggests widespread global distribution of PFOS including remote locations.

Alkanesulfonic Acids↗

Global distribution of perfluorooctane sulfonate in wildlife.

Here we report, for the first time, on the global distribution of perfluorooctanesulfonate (PFOS), a fluorinated organic contaminant. PFOS was measured in the tissues of wildlife, including, fish, birds, and marine mammals. Some of the species studied include bald eagles, polar bears, albatrosses, and various species of seals. Samples were collected from urbanized areas in North America, especially the Great Lakes region and coastal marine areas and rivers, and Europe. Samples were also collected from a number of more remote, less urbanized locations such as the Arctic and the North Pacific Oceans. The results demonstrated that PFOS is widespread in the environment. Concentrations of PFOS in animals from relatively more populated and industrialized regions, such as the North American Great Lakes, Baltic Sea, and Mediterranean Sea,were greaterthan those in animals from remote marine locations. Fish-eating, predatory animals such as mink and bald eagles contained concentrations of PFOS that were greater than the concentrations in their diets. This suggests that PFOS can bioaccumulate to higher trophic levels of the food chain. Currently available data indicate that the concentrations of PFOS in wildlife are less than those required to cause adverse effects in laboratory animals.

Animals↗

Polychlorinated naphthalenes, -biphenyls, -dibenzo-p-dioxins, and -dibenzofurans in double-crested cormorants and herring gulls from Michigan waters of the Great Lakes.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), naphthalenes (PCNs), and biphenyls (PCBs) were measured in eggs of double-crested cormorants and herring gulls collected from Michigan waters of the Great Lakes. Concentrations of PCNs in eggs of double-crested cormorants and herring gulls were in the ranges of 380-2400 and 83-1300 pg/g, wet wt, respectively. Concentrations of 2,3,7,8-substituted PCDDs and PCDFs were 10-200 times less than those of PCNs in eggs whereas those of total PCBs (380-7900 ng/g, wet wt) were 3-4 orders of magnitude greater. While the profile of PCB isomers and congeners between double-crested cormorants and herring gulls was similar, the PCN isomer profile differed markedly between these two species. PCN congeners 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) accounted for greater than 90% of the total PCN concentrations in herring gulls, whereas their contribution to total PCN concentrations in double-crested cormorants ranged from 18 to 40% (mean, 31%). The ratios of concentrations of PCDDs to PCDFs were greater in herring gulls than in double-crested cormorants collected from the same locations, suggesting the ability of the former to metabolize PCDF congeners relatively rapidly. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) contributed by PCNs in double-crested cormorant and herring gull eggs were 2-3% of the sum TEQs of PCBs, PCDDs, PCDFs, and PCNs. PCB congener 126 (3,3',4,4',5-PeCB) accounted for 57-72% of the total TEQs in double-crested cormorant and herring gull eggs.

Animals↗

Identification and quantitation of nonylphenol ethoxylates and nonylphenol in fish tissues from Michigan.

Nonylphenol (NP) and its lower ethoxylates, nonylphenol monoethoxylate (NPE1) and nonylphenol diethoxylate (NPE2), can be present in aquatic environments at total concentrations of more than 10 microg/L. They are metabolites of nonylphenol polyethoxylates (NPE) and have been found to be weakly estrogenic. To evaluate bioaccumulation potential and identify potential risks posed by these chemicals, concentrations of NP, NPE1, NPE2, and nonylphenol triethoxylate (NPE3) were determined in the tissues of fish inhabiting various waters in Michigan. This method involves extraction of samples using exhaustive steam distillation with concurrent liquid extraction. Concentrations of NP among all sites and species ranged from <3.3 to 29.1 ng/g, ww and varied little among sites. NPE1 was detectable in some samples but at concentrations less than the method detection limit (16.8 ng/g). Concentrations of NPE2 and NPE3 in all samples were less than their respective MDLs of 18.2 and 20.6 ng/g.

Animals↗

Accumulation of organochlorine pesticides and polychlorinated biphenyls in sediments, aquatic organisms, birds, bird eggs and bat collected from south India.

Concentrations of polychlorinated biphenyls (PCBs), DDT and its metabolites (DDTs), HCH isomers (HCHs), chlordane compounds (CHLs) and hexachlorobenzene (HCB) were determined in sediment, soil, whole body homogenates of resident and migratory birds and their prey items (including fish, green mussel, snail, earthworm, crabs, prawn, lizard and frogs), bird eggs and bats collected from southern India during 1995 and 1998. Accumulation pattern of organochlorines (OCs) in biota was, in general, in the order, HCHs > DDTs > PCBs > CHLs = HCB. Magnitude of OC concentrations increased in the order of sediments < green mussel < earthworm < from < lizard < fish < bird egg < bats < birds tissues. Biomagnification features of OCs were examined in resident and migrant birds to evaluate the exposure levels of these chemicals in wintering grounds of migrant birds. Accumulation of DDTs in migratory birds during wintering in India may be of concern due to the great biomagnification potential of DDTs. Eggs of some resident species contained noticeable concentrations of OCs. Concentrations of OCs in three species of bats analyzed in this study were lower than that found in passerine birds. In addition to OCs, butyltin compounds were also detected at low concentrations in bats.

Animals↗

Trace organic contaminants in sediment and water from Ulsan Bay and its vicinity, Korea.

Sediment and water samples collected from 32 locations in Ulsan Bay and adjacent inland areas were analyzed for polycyclic aromatic hydrocabons (PAHs), nonylphenol (NP), octylphenol (OP), bisphenol A (BPA), organochlorine (OC) pesticides (HCB, HCHs, CHLs, and DDTs), and polychlorinated biphenyls (PCBs) to characterize their spatial distribution and contamination status. PAHs were detected in nearly all sediment and water extracts from Ulsan Bay and its inland locations. The sedimentary PAH concentrations ranged from 17 to 3,100 ng/g on a dry weight basis (DW), which were predominated by two- and three-ring aromatic hydrocarbons in river and/or stream, and four- to six-ring compounds in Ulsan Bay sediment. Concentrations of PAHs in pore water samples were generally two or three orders magnitude less than those of corresponding sediment samples. Maximum concentrations of NP, OP, and BPA in sediments were 1,040, 120, and 54 ng/g DW, respectively. Concentrations of OP and BPA were, on average, 5- to 13-fold less than those of NP. PCB concentrations in sediment ranged from 1.4 to 77 ng/g DW, which were predominated by lower chlorinated congeners such as di- through pentachlorinated biphenyls. Among different OC pesticides analyzed, concentrations of DDTs were the greatest, ranging from 0.02 to 41.9 ng/g DW. NP concentrations were greater at inner locations proximal to municipal wastewater discharges into rivers and/or streams, whereas the concentrations of PCBs and PAHs were great near the sites of high industrial activities. Sediment-pore water partitioning coefficients correlated with those of reported Koc or Kow values for selected PAHs in Ulsan Bay, but these varied by an order of magnitude for stream and/or river sediments.

Chromatography, Gas↗

In vitro bioassay determination of dioxin-like and estrogenic activity in sediment and water from Ulsan Bay and its vicinity, Korea.

Extracts of sediment and water samples collected from Ulsan Bay, Korea, were screened for their ability to induce dioxin-like and estrogenic gene expression in vitro. Each sample was tested as raw extract (RE) and fractionated extract (FE). Based on the initial screening of RE, 23 of 31 sediment samples showed significant dioxin-like activity in H4IIE-luc bioassay, whereas most sediment samples did not elicit estrogenic response in MVLN bioassay. Most of the activities associated with FE samples revealed that mid-polar (F2) and most polar (F3) fractions were responsible for the significant reporter gene expression in H4IIE-luc bioassay. The results suggest that complex interactions may have depressed the activities of the known arylhydrocarbon receptor (AhR) agonists present in F1 samples. The F2 samples were the most active fraction. All F2 samples except one induced significant dioxin-like activity, and over half of the F2 samples induced significant estrogenic activity. Ten of the F2 samples produced magnitudes of response in H4IIE-luc bioassay similar to those induced by a 2,3,7,8-tetrachlorodibenzo-p-dioxin standard. Sediment associated with F2 samples was estimated to contain 24.9-826 pg TCDD-EQ/g DW. Based on a qualitative mass balance analysis, polycyclic aromatic hydrocarbons (PAHs) appeared to account for both the estrogenic and dioxin-like responses observed. Over half of the F3 samples were either cytotoxic or caused morphological changes in both H4IIE-luc and MVLN cells. Known concentrations of alkylphenols and bisphenol A were not great enough to account for both the estrogenic response and cytotoxicity observed for F3 samples. Despite the apparent toxic or stressful effects, most of F3 samples induced significant dioxin-like activity in vitro, adding to a growing body of evidence that suggests the presence of unidentified, relatively polar, AhR agonists in sediment from some areas.

Animals↗

Organochlorine pesticides, polychlorinated biphenyls, and butyltin compounds in blubber and livers of stranded California sea lions, elephant seals, and harbor seals from coastal California, USA.

Concentrations of polychlorinated biphenyls (PCBs), DDTs (p,p'-DDE, p,p'-DDD, p,p'-DDT), chlordanes (CHLs; cis-chlordane, cis-nonachlor, trans-nonachlor, and oxychlordane), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and mono- (MBT), di-(DBT), and tri-butyltin (TBT) were determined in blubber and livers of 15 California sea lions (Zalophus californianus), 6 northern elephant seals (Mirounga augustirostris), and 10 harbor seals (Phoca vitulina) found stranded along the coasts of California, USA, during 1991-1997. Among the organochlorines analyzed, DDTs were predominant, followed in decreasing order by PCBs, CHLs, TCPMe, TCPMOH, HCHs, and HCB. The greatest concentrations of organochlorines were found in California sea lions. The highest DDT and PCB concentrations found in the blubber of California sea lions were 2,900 and 1,300 microg/g, lipid weight, respectively. Concentrations of TCPMe and TCPMOH in California sea lions were correlated significantly with DDT concentrations. Concentration ratios of various organochlorines in harbor seal livers were different from those in California sea lions and elephant seals, which suggested that the sources of exposure of harbor seals to organochlorines were different from those in the other two species. Concentrations of butyltin compounds in livers of pinniped species ranged from 2 to 99 ng/g, wet weight, which were less than those observed in cetaceans and in California sea otters.

Adipose Tissue↗

Multi-elemental concentrations in tissues of Japanese common squid (Todarodes pacificus).

Forty-five elements were determined in mantle muscle and liver of juvenile Japanese common squid, Todarodes pacificus, collected from three locations in and near Japanese coasts, using a high-resolution inductively coupled plasma mass spectrometer (HR-ICP-MS) and an inductively coupled plasma atomic emission spectroscope (ICP-AES). Multivariate statistical techniques were applied to discriminate populations of squids from these three locations by treating absolute and relative concentrations of trace elements. Significant differences were found in the concentrations of elements, particularly for some alkaline and alkaline earth elements in the muscle and liver and for some 3d transition elements in the liver of three groups of squids. Squids from the Pacific Ocean could be distinguished from those of the Sea of Japan by discriminant function analysis of elemental concentrations. Based on the analysis, the squids collected from the Nemuro Strait in Japan were predicted to belong to those from the Sea of Japan. Elemental concentrations and discriminant function analysis can be used to identify subpopulations and migratory routes of squids.

Animals↗

Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats.

Some environmental contaminants have the potential to affect humans or animals by mimicking the effects of hormones. Bisphenol A (BPA) is a weak estrogen agonist when tested using in vitro or in vivo bioassays. In addition to the well documented effects of estrogens on reproductive functions, ovarian hormones also have salient effects on mammalian energy balance and feeding behavior. In this study, we investigated the effects of BPA on body weight and food intake of ovariectomized adult female rats. Treatment with doses of 4 or 5 mg/day for 15 days resulted in a significant reduction of body weight gain with no reduction in food intake. A dose of 1 mg/day did not affect feeding or weight gain. BPA was detected in the blood, brain and adipose tissues of the BPA-treated animals but not in the vehicle control group. There was a preferential concentration of BPA in brown adipose tissue. These results indicate that BPA can affect energy balance and that brown adipose tissue may be a primary tissue into which BPA accumulates in mammals.

Adipose Tissue↗

Organochlorine insecticides, polychlorinated biphenyls, and metals in water, sediment, and green frogs from southwestern Michigan.

In an attempt to explain the etiology of frog deformities and population declines, many possible causative factors have been examined, including the input of synthetic chemicals into aquatic systems, where frogs spend much of their lives, including their entire developmental stages. Deformities in populations of green frogs in wetlands of southwestern Michigan that are influenced by agricultural, urban, or industrial inputs were assessed in this study. Of the 1445 green frogs (Rana clamitans) examined, only four (0.3%) exhibited morphological deformities. This deformity rate is less than the recognized background level of deformities for this species, which is approximately 1%. Concentrations of organochlorine insecticides, polychlorinated biphenyls (PCBs), and metals were determined in water, sediment, frog eggs, tadpoles, and adult green frog tissues. Concentrations of all individual organochlorine insecticides in tissue were less than 6 ng/g, wet wt. Concentrations of sigmaPCBs in tissue did not exceed 100 ng/g, wet wt. Concentrations of toxic metals were less than the limits of detection. Because no significant numbers of green frog deformities were observed in this region, it can be assumed that at these low concentrations, physical malformations in green frogs should not be observed. Significance of study. This study provides information on the incidence of deformities in green frog populations in southwestern Michigan and offers background data on chemical residues in green frogs and their environment.

Animals↗

In vitro response of fish and mammalian cells to complex mixtures of polychlorinated naphthalenes, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons.

In vitro characterization and comparison of responses to different classes of biologically active compounds can increase the utility of bioassays. In this study, the relative potencies (REPs) of mixtures of polychlorinated naphthalenes (PCNs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs), to induce in vitro ethoxyresorufin-O-deethylase (EROD) in PLHC-1 fish hepatoma cells, H4IIE wild type (H4IIE-wt) rat hepatoma cells, and recombinant H4IIE cells (H4IIE-EROD) were determined. The mixtures were also analyzed by in vitro luciferase assay with recombinant H4IIE cells (H4IIE-luc). Halowaxes 1051, 1014, and 1013 caused significant induction in all three H4IIE assays at concentrations less than 10 mg/l, but did not elicit a significant response in the PLHC-1 assay. Based on H4IIE results, the Halowaxes were estimated to have relative potencies (REPs) of approximately 10(-6)-10(-8) relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Less than 5 mg/l of Aroclors 1242, 1248, 1254; Clophens A60, T64; and Chlorofen induced significant responses in the H4IIE assays, while only Clophens A60 and T64 caused a significant response in the PLHC-1 assay. The efficacy of the Aroclor mixtures was generally insufficient to allow for quantitative REP estimates, but, based on their responses in the H4IIE assays, Clophen A60 and Chlorofen were estimated to have REPs of approximately 10(-6) and 10(-7), respectively. A mixture of 16 priority PAHs caused significant induction in all four cell types and was estimated to have a REP of approximately 10(-4). Overall, the results of this study add to a growing database on the dioxin-like potency of complex mixtures of xenobiotics, and suggested that H4IIE-based in vitro bioassays were more sensitive than PLHC-1 cells for detecting dioxin-like activity in complex mixtures.

Animals↗

Mutational analysis of the candidate tumor suppressor gene ING1 in Indian oral squamous cell carcinoma.

ING1, a recently identified candidate tumor suppressor gene, involved in the p53 signaling pathway is mapped at chromosome 13q34. Since loss of heterozygosity at 13q34 has been reported in squamous cell carcinoma of head and neck, we screened for mutations in ING1 by polymerase chain reaction-single strand conformation polymorphism in 71 oral squamous cell carcinomas (OSCC) from India, 15 of which were known to harbor p53 mutations. A single polymorphism (G to A) was detected in 14 (19.7%) of the tumors analyzed. No mutation was observed in any of the 71 OSCCs analyzed. These results suggest that ING1 is not a target for mutational inactivation in OSCC of Indians.

Areca↗