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At least 1,405 records · Page 78Linked to original sources
PubMed1994

Pharmacological profile of a non-peptidic dual inhibitor of neutral endopeptidase 24.11 and endothelin-converting enzyme.

CGS 26303 is a potent and structurally unique non-peptidic inhibitor of neutral endopeptidase (NEP) capable of protecting atrial natriuretic peptide (ANP) from enzymatic degradation. In addition, CGS 26303 displays modest endothelin-converting enzyme (ECE) inhibitory activity in vitro. Unlike CGS 24592, a potent but selective NEP inhibitor, CGS 26303 significantly blocks endothelin-1 production in rats after exogenous administration of big ET-1 and reduces the mean arterial pressure in spontaneously hypertensive rats during chronic administration. These results suggest that CGS 26303 represents a new class of therapeutic agents with potential benefits for the treatment of cardiovascular and renal disorders.

Amino Acid Sequence↗
PubMed1994

Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons.

Defects in the gene encoding the endothelin-B receptor produce aganglionic megacolon and pigmentary disorders in mice and humans. We report that a targeted disruption of the mouse endothelin-3 ligand (EDN3) gene produces a similar recessive phenotype of megacolon and coat color spotting. A natural recessive mutation that results in the same developmental defects in mice, lethal spotting (ls), failed to complement the targeted EDN3 allele. The ls mice carry a point mutation of the EDN3 gene, which replaces the Arg residue at the C-terminus of the inactive intermediate big EDN3 with a Trp residue. This mutation prevents the proteolytic activation of big EDN3 by ECE-1. These findings indicate that interaction of EDN3 with the endothelin-B receptor is essential in the development of neural crest-derived cell lineages. We postulate that defects in the human EDN3 gene may cause Hirschsprung's disease.

Amino Acid Sequence↗
PubMed1991

cDNA cloning, sequence analysis and tissue distribution of a precursor for vasoactive intestinal contractor (VIC).

A full-length cDNA encoding preprovasoactive intestinal contractor (PPVIC) has been cloned. From the deduced 160 amino acid PPVIC, the mature VIC is predicted to be produced via a 37 residue intermediate, big VIC. The PPVIC also contains a VIC-like peptide of 16 amino acids structurally related to to the amino-terminal residues of VIC and flanked by pairs of dibasic amino acids, putative processing sites. RNA blot hybridization with PPVIC cDNA confirmed the PPVIC gene to be expressed in the small and large intestinal tract in a tissue specific manner.

Amino Acid Sequence↗
PubMed1999

Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme.

We have determined the nucleotide sequence of the clone pAL2 obtained from Porphyromonas gingivalis 381 in the previous study [Ansai et al. (1995) Microbiology 141, 2047-20521. The DNA sequence analysis of this fragment revealed one complete ORF and one incomplete ORF. The ORF encoded a protein (PgPepO) of 690 amino acids with a calculated molecular weight of 78796. The deduced amino acid sequence exhibited a significant homology with human endothelin-converting enzyme (ECE)-1. Recombinant PgPepO was purified to homogeneity and characterized. The purified enzyme was strongly inhibited by phosphoramidon, and converted big endothelin-1 to endothelin-1. Furthermore, the purified PgPepO strongly cross-reacted with a monoclonal antibody against rat ECE-1. These results indicate that PgPepO has striking similarity to mammalian ECE in structure and function.

Amino Acid Sequence↗
PubMed1990

Non-mammalian "big" neurophysins--complete amino acid sequence of a two-domain MSEL-neurophysin from goose.

Vasotocin-associated neurophysin (MSEL-neurophysin) has been purified from goose neurohypophysis through molecular sieving and high-pressure reverse-phase liquid chromatography (HPLC). The protein has a molecular mass (measured by SDS-polyacrylamide gel electrophoresis) of 17 kDa in contrast to 10 kDa found for the mammalian MSEL-neurophysins. Complete amino acid sequence (131 residues) has been determined mainly through tryptic or staphylococcal proteinase peptides derived from carboxyamidomethylated neurophysin, isolated by HPLC and microsequenced. N- and C-terminal sequences have been established by Edman degradation or action of carboxypeptidase Y, respectively, applied on the native protein. Goose MSEL-neurophysin is homologous to the two-domain "big" MSEL-neurophysin previously identified in the frog. It appears that in non-mammalian tetrapods, namely birds and amphibians, the proteolytic processing of the pro-vasotocin involves only one cleavage, releasing the hormone moiety and a "big" neurophysin with two domains homologous to mammalian MSEL-neurophysin and copeptin, respectively. Comparison of the avian protein with its mammalian and amphibian counterparts reveals that the first half of the polypeptide chain is evolutionarily much less variable than the second and that the goose protein resembles the frog protein much more than the mammalian one.

Amino Acid Sequence↗
PubMed1996

Characterization of the gene encoding the human LW blood group protein in LW+ and LW- phenotypes.

The LW blood group is carried by a 42-kD glycoprotein that belongs to the family of intercellular adhesion molecules. The LW gene is organized into three exons spanning an HindIII fragment of approximately 2.65 kb. The exon/intron architecture correlates to the structural domains of the protein and resembles that of other Ig superfamily members except that the signal peptide and the first Ig-like domain are encoded by the first exon. The 5'UT region (nucleotides -289 to +9) includes potential binding sites for various transcription factors (Ets, CACC, SP1, GATA-1, AP2) and exhibited a significant transcriptional activity after transfection in the erythroleukemic K562 cells. No obvious abnormality of the LW gene, including the 5'UT region, has been detected by sequencing polymerase chain reaction-amplified genomic DNA from RhD+ or RhD- donors and from an Rhnull variant that lacks the Rh and LW proteins on red blood cells. However, a deletion of 10 bp in exon 1 of the LW gene was identified in the genome of an LW (a- b-) individual (Big) deficient for LW antigens but carrying a normal Rh phenotype. The 10-bp deletion generates a premature stop codon and encodes a truncated protein without transmembrane and cytoplasmic domain. No detectable abnormality of the LW gene or transcript could be detected in another LW(a- b-) individual (Nic), suggesting the heterogeneity of these phenotypes.

Amino Acid Sequence↗
PubMed2005

Endothelin-1 as a central mediator of LPS-induced fever in rats.

Fever induced by E. coli lipopolysaccharide (LPS) in rats is substantially reduced by blockade of central endothelin ET(B) receptors. This study explores the role of endothelin-1 as a central mediator of fever in rats, by investigating the effect of a pyrogenic dose of LPS on the levels of big endothelin-1 and endothelin-1 in the cerebrospinal fluid (CSF) and endothelin-1 in the plasma. We further assessed whether the increase in body temperature caused by central injection of endothelin-1 constitutes solely a hyperthermia or a true integrated febrile response. LPS (5 mug kg(-1), i.v.) induced fever which peaked at 1.16 +/- 0.24 degrees C within 2 h and remained stable up to 5 h. CSF levels of immunoreactive (ir) big endothelin-1 decreased to undetectable levels at 3 h after LPS, returning only partially at 5 h post-injection. CSF ir-endothelin-1 levels were undetectable in saline-treated animals, but reached 21.9 +/- 5.2 fmol ml(-1) at 3 h after LPS treatment. Plasma ir-endothelin-1 levels were unchanged after saline or LPS. Central injection of endothelin-1 (1 pmol, i.c.v.) caused long-lasting increases in body temperature (0.81 +/- 0.17 degrees C, 3 h), but simultaneously decreased tail skin temperature (-1.10 +/- 0.26 degrees C), indicating cutaneous vasoconstriction. Moreover, endothelin-1 induced fever (1.0 +/- 0.3 degrees C, 3 h) when injected into the preoptic area of the anterior hypothalamus (100 fmol), but not i.v. (1 or 10 pmol). These data suggest that endothelin-1 is produced in the brain and acts centrally as a mediator of LPS-induced fever.

Animals↗
PubMed1999

Spontaneous mutation frequency and pattern in Big Blue mice fed a vitamin E-supplemented diet.

Endogenous oxidative DNA damage caused by normal cellular processes may play a vital role in carcinogenesis. To directly test the hypothesis that antioxidants will protect DNA from oxidative damage in vivo, Big Blue((R)) mice were fed either a control diet (66 IU vitamin E/kg diet) or a high-dose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,l-alpha-tocopherol acetate from conception until 3 months of age. Using the standard Big Blue((R)) protocol, 15.5 million plaque forming units (pfu) were examined from five tissues (heart, liver, adipose tissue, thymus, and testis) of three control and three high-dose vitamin E supplemented male mice generating 433 mutants, which represented 373 independent mutations upon sequencing the lacI transgene. The alpha-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed little if any with vitamin E supplementation. In adipose tissue, which accumulated the highest levels of vitamin E, mutation frequency was significantly reduced with high-dose vitamin E supplementation (P = 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P = 0.40). When data from all tissues were combined, a reduction in G:C --> T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d-alpha-tocopherol acetate.

Animals↗
PubMed1998

Echo SPL, training experience, and experimental procedure influence the ranging performance in the big brown bat, Eptesicus fuscus.

Four Eptesicus fuscus were trained in a range discrimination experiment to choose the closer of two phantom targets. Echo attenuation was roving between trials returning echoes ranging from -10 dB to -50 dB SPL (sound pressure level) relative to emission SPL. Discrimination thresholds were determined. After sufficient training, ranging performance was stable and about the same in the range between -20 dB and -50 dB with range difference thresholds around 300 microseconds. At -10 dB, performance was poor even after long training. After additional training at a constant relative echo SPL of -30 dB and a delay difference of 300 microseconds the performance measured with roving echo SPL improved at all relative echo SPL between -20 dB and -50 dB but not at -10 dB. The new experimental procedure improved the performance by additional learning, and the bats generalized over a wide range of relative echo SPL. Threshold improved to 100 microseconds when measured at a constant relative echo SPL of -30 dB, again indicating the influence of the experimental procedure. In correspondence to neurophysiological data the ranging performance deteriorates if the echo SPL is close to the emission SPL. Signal duration and emission SPL were variable during range discrimination.

Animals↗
PubMed1991

Muscular mechanical energy expenditure as a process for detecting potential risks in manual materials handling.

The problem of injuries in manual materials handling remains a big concern in industrialized countries. It has become imperative in occupational biomechanics to extend the analyses to all pertinent factors involved in working tasks and to adopt an experimental approach leading to the understanding of the relative demands imposed simultaneously on all body joints. The evaluation of joint muscular work and the processes of energy generation, absorption and transfer appears promising as a tool in the detection of risk factors in working tasks. The present study consisted of evaluating two tasks (lifting and lowering) performed at five different heights (from 15 to 185 cm) with five different loads (from 3.3 to 22.0 kg). The subjects were eight experienced workers from a food product warehouse. Cinematography techniques and two AMTI force platforms were used to collect the data. Dynamic and planar segmental analyses were performed to calculate the net muscular moments at the joints, and work was calculated from the integration of muscular power. Factorial analyses of variance with repeated measures were performed on the dependent variables to evaluate the main effects of tasks, loads, and heights (for lifting and for lowering) and the interactions. The results revealed the adoption of different movement strategies in the handling of heavier loads. In the first, a larger emphasis of energy transfer and movement economy; in the second, a reduction in the relative contribution of the shoulders to the detriment of an increased participation of the lower back and hips was found. The comparison between lifting and lowering tasks indicated that lifting was only slightly more demanding than lowering for maximum muscular moments (about 15%) but much more so for mechanical work (about 40%); however, the nature of the efforts in eccentric contractions suggests that the lowering of heavy loads may be risky. Finally, the results revealed the deviation of height of handling from the waist level to be a significant factor. Handling at lower heights was considerably more demanding but the work was shared by several joints, mainly by the hips and lower back (about 70%); on the other hand, in handling above the waist, the work efforts were concentrated on the upper limbs (about 80%). In most cases, the participation of lower limbs was minimal and some movement strategies are suggested for future research.

Accidents, Occupational↗
PubMed2001

Facile solid-phase synthesis of sulfated tyrosine-containing peptides: total synthesis of human big gastrin-II and cholecystokinin (CCK)-39.

Chemical synthesis of tyrosine O-sulfated peptides is still a laborious task for peptide chemists because of the intrinsic acid-lability of the sulfate moiety. An efficient cleavage/deprotection procedure without loss of the sulfate is the critical difficulty remaining to be solved for fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase synthesis of sulfated peptides. To overcome the difficulty, TFA-mediated solvolysis rates of a tyrosine O-sulfate [Tyr(SO3H)] residue and two protecting groups, tBu for the hydroxyl group of Ser and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) for the guanidino group of Arg, were examined in detail. The desulfation obeyed first-order kinetics with a large entropy (59.6 J.K-1.mol-1) and enthalpy (110.5 kJ.mol-1) of activation. These values substantiated that the desulfation rate of the rigidly solvated Tyr(SO3H) residue was strongly temperature-dependent. By contrast, the SN1-type deprotections were less temperature-dependent and proceeded smoothly in TFA of a high ionizing power. Based on the large rate difference between the desulfation and the SN1-type deprotections in cold TFA, an efficient deprotection protocol for the sulfated peptides was developed. Our synthetic strategy for Tyr(SO3H)-containing peptides with this effective deprotection protocol is as follows: (i) a sulfated peptide chain is directly constructed on 2-chlorotrityl resin with Fmoc-based solid-phase chemistry using Fmoc-Tyr(SO3Na)-OH as a building block; (ii) the protected peptide-resin is treated with 90% aqueous TFA at 0 degree C for an appropriate period of time for the cleavage and deprotection. Human cholecystokinin (CCK)-12, mini gastrin-II (14 residues), and little gastrin-II (17 residues) were synthesized with this method in 26-38% yields without any difficulties. This method was further applied to the stepwise synthesis of human big gastrin-II (34 residues), CCK-33 and -39. Despite the prolonged acid treatment (15-18 h at 0 degree C), the ratios of the desulfated peptides were less than 15%, and the pure sulfated peptides were obtained in around 10% yields.

Amino Acid Sequence↗
PubMed2003

[Selection of a peptide mimic the neutralization epitope of hepatitis E virus with phage peptide display technology].

Hepatitis E is an acute hepatitis casused by hepatitis E virus (HEV) in developing countries, where it occurs as cases sporadic and in epidemics form. The causative agent, hepatitis E virus, is transmitted primarily by the fecal-oral route. HEV is icosahedron non-enveloped virus, and its genome is a single-stranded, positive-sense, 3'-polyadenylated RNA about 7.5 kb in length. It contains three open reading frames (ORFs). Of which ORF1 codes for a polyprotein of 1693 amino acids and contain domains homologous to a viral methyltransferase, a papainlike cysteine protease, an RNA helicasre, and an RNA-dependent RNA polymerase, besides the most hypervariable region of the HEV genome. And ORF3 codes for a 123-amino-acide-long polypeptide with unknown function. While the major viral capsid protein (pORF2, ORF2 codes) of 660 amino acid was showed to contain the protective epitope. The bacterially expressed polypeptide disignated as NE2 has been proved to be a protective antige. And the anti-NE2 monoclonal antibodies (mAb) was screend, two of these mAbs 8C11 and 8H3 were showed to be against separate conformational neutralization epitope of hepatitis E virus (HEV). And these two mAb were used to screen for binding peptides from a 7-peptides phage display library. After four rounds of panning, tweenty-one positive monoclonal phages (11 for 8C11, and 10 for 8H3) were selected and the inserted fragments were sequenced. The DNA sequence coding for the obtained dominant peptide 8C11 (N'-His-Pro-Thr-Leu-Leu-Arg-Ile-C', named 8C11A) and 8H3 (N'-Ser-Ile-Leu-Pro-Tyr-Pro-Tyr-C', named 8H3A) were then synthesized and cloned to insert between amino acid 78 to 83 of hepatitis B core antigen (HBcAg), then expressed in E. coli. The recombinant proteins aggregate into homodimer or polymer on SDS-PAGE, and could bind with mAb 8C11 and 8H3 in Western blotting. Respectively, the recombinant protein C8C11A showed to be dimer mainly, which can bind with mAb 8C11. The monomer and dimer of C8H3A are in the same amount on SDS-PAGE, but only the dimer could bind with mAb 8H3 on Western blotting. The renatured recombinant proteins were all showed to aggregate into virus like particles which were similar as HBcAg on transmission electron micrograph. The dominant peptide 8H3A (N'-Ser-Ile-Leu-Pro-Tyr-ProTyr-C') that selected out by mAb 8H3 was further chemo-synthesized, and its binding activity was confirmed by BIAcore biosensor. The result showed that this 7-peptide can bind with mAb 8H3 in a big Ka and Kd form, which means the binding is not stable. These results implicated that conformational dependent neutralization epitope could be partially modeled by short peptide, which provided a feasible route for subunit vaccine development.

Amino Acid Sequence↗
PubMed2005

[Overweight among eight and twelve-year-old children in Oslo in 2004].

BACKGROUND: Overweight among children is an increasing problem internationally. The body mass index of the parents and their children influences body mass index during adulthood and the probability of overweight and obesity. The aim of this survey was to obtain reliable data on weight and height for eight and twelve-year-olds in Oslo. MATERIAL AND METHODS: School health nurses in Oslo took measurements of the children's weight and height. The survey includes 3453 eight-year-olds and 3597 twelve-year-olds. RESULTS: The prevalence of overweight among eight-to-twelve-year-olds is 21%. There is a significant difference in the prevalence of overweight children between the local districts of Oslo. One in four of eight-year-old and one in five of twelve-year old girls are overweight. There is no significant difference between boys in different age groups. INTERPRETATION: The prevalence of overweight among eight to twelve-year-old children in Oslo is alarming. There are big differences between districts.

Adult↗
PubMed2005

Evaluation of internal adaptation in ceramic and composite resin inlays by silicon replica technique.

This study was aimed at investigating the internal adaptation of a ceramic (Ceramco II) and two composite resin inlay materials (SureFil and 3M Filtek Z 250) using silicon replica technique as an indicator. Forty-five standard mesial-occlusal-distal (MOD) cavities were prepared into brass moulds by using computer numerically controlled system. Inlays were prepared according to manufacturers' instructions with indirect methods. Replicas of the prepared cavities and inlays were produced with a polyvinyl siloxane material (Elite H-D). The spaces between inlays and cavities were filled by different coloured light-body polyvinyl siloxane material. Two parallel slices (mesio-distally) were obtained from the replicas with a sharp blade. Different coloured polyvinyl siloxane material thickness between cavity and inlay was measured at seven points (mesial, occlusal and distal). The data were evaluated with anova and Tukey's honestly significantly different (HSD) statistical tests. In the SureFil and Ceramco II groups, the sizes of the contraction gaps at mesial and distal gingival floors were greater than that of the occlusal marginal walls. In comparison of gap formation at occlusal regions, while the 3M composite group showed highest gap values (204.33 +/- 75.45 microm), the Ceramco II group revealed the lowest (141.17 +/- 23.66 microm) (P < 0.05). At the gingival floors, gap formation of Ceramco II group was the highest (227.08 +/- 51.95 microm). Neither the 3M Filtek Z250 nor SureFil group showed any statistical difference between gap values of their self-occlusal and gingival floors (P > 0.05). In conclusion, our results showed that ceramic inlays did not confer any big advantage for internal adaptation over the composite inlays.

Ceramics↗
PubMed2005

The changes in taste preferences during 4 years period of methadone maintenance treatment.

The aim of the study was the analysis of the changes in the kind and the frequency of particular nutritional products consumption by opiate addicted persons during 4-year lasting methadone programme. There were 30 opiate addicted patients under examination (23 men and 7 women). Food consumption quality was estimated with the use of the Intake Frequency of Food Products Questionnaire. The examinations were performed before methadone administration had started, after 9 months and after 4 years of methadone maintenance treatment. Three categories of consumption frequency were established: rarely, moderately and often. The classification of different products was done with the use of hierarchic cluster analysis. For general illustration of the data the consumed products were compared by the means of hierarchical cluster analysis (this was done with the help of Euclidean distances and the Ward's algorithm). Then the k-means (with k=3) method was used in order to identify groups of products that were similarly often consumed. Each k-means analysis was performed separately for each examination. This was done in order to find out the products that change the cluster from one examination to another. Twenty labile products were identified. The examined products were moving between the adherent categories. This means that the consumption pattern undergoes some changes over the course of methadone therapy. Additionally, the analysis of the diet of this group of people shows improper and unhealthy nutritional behaviours: too big intake of sweets and too low intake of complex carbohydrates, fish and vegetable fats. This was especially visible at the beginning of the therapy, later this unfavourable diet habits changed but not to the desired level.

Adult↗
PubMed1994

The Enterococcus faecalis extracellular metalloendopeptidase (EC 3.4.24.30; coccolysin) inactivates human endothelin at bonds involving hydrophobic amino acid residues.

The extracellular metalloendopeptidase (EC 3.4.24.30; coccolysin) from Enterococcus faecalis (Strain OG1-10) inactivates human endothelin-1 by hydrolyzing the peptide primarily at the Ser5-Leu6 and the His16-Leu17 bonds and the human big endothelin at several bonds involving hydrophobic amino acid residues. The big endothelin fragment 22-38 was also hydrolyzed at a high rate. The degradation of endothelin by coccolysin resembles the peptidolytic processing of endothelin by thermolysin. Because E. faecalis is associated with a large number of infectious diseases, it is possible that the manifestation of inflammatory conditions in the presence of this organism is related to the coccolysin-catalyzed inactivation of endothelin.

Amino Acid Sequence↗
PubMed2003

Trauma registry in Tikur Anbessa Hospital, Addis Ababa, Ethiopia.

A simplified trauma registry was tested in Tikur anbessa hospital, with the aim of obtaining preliminary data on the patterns and magnitude of injuries and establishing the basis towards surveillance system. All injured patients presented to the surgical and pediatric emergency department between January 1, 1999 and June 31, 1999 were included. Interns completed the registry forms, which include demographic, injury event specific, severity and outcome data. The severity was assessed by new scoring system, Kampla Trauma Score (KTS). Among the 3822 injured patients 2869(75%) were males and 953(25%) were females and 80% were below the age of 40 years. 77% of the injuries were unintentional and motor vehicle injuries accounted for 41% of all causes among which 93% of them were pedestrians. Accidental fall and interpersonal assault accounted for 21% and 20% respectively. Admitted cases were 11.6%, while 20 (.5%) died at the outpatient department with the overall mortality of 1.47%. Though burn and gunshot accounted only for 6%, the case fatality rate was highest (4%) accounting for 20% of all deaths. The magnitude of fatal injuries is underestimated and the pattern of injuries may only reflect the situation in the big cities. Motor vehicle injuries, especially pedestrian injuries are serious problem in Addis as seen in patients in Tikur Anbessa hospital and require further situational studies and urgent intervention. Establishing hospital based simplified injury surveillance system is possible in Ethiopia and it is essential to asses the magnitude of the problem and identify priority area for injury prevention and control.

Adolescent↗
PubMed1996

Assessment of 1,3-butadiene mutagenicity in the bone marrow of B6C3F1 lacI transgenic mice (Big Blue): a review of mutational spectrum and lacI mutant frequency after a 5-day 625 ppm 1,3-butadiene exposure.

1,3-Butadiene (BD) is a carcinogen that is bioactivated to at least two genotoxic metabolites. In the present article, we review briefly our previous studies on the in vivo mutagenicity and mutational spectra of BD in bone marrow and extend these studies to examine the effect of exposure time (5-days vs. 4-week exposure to 625 ppm BD used in previous studies) on the lacI mutant frequency in the bone marrow. Inhalation exposure to BD at 625 ppm and 1,250 ppm mutagenic in vivo, inducing an increase in the transgene mutant and mutation frequency in the bone marrow. Analysis of the mutational spectrum in BD-exposed and air control mice demonstrated that BD exposure induced an increased frequency of mutations at A:T base pairs. There was no difference in the lacI mutant frequency determined in the bone marrow between a short-term exposure to BD (5 days) and a longer-term exposure (4 weeks). These data taken together demonstrate that inhalation exposure to BD induces in vivo somatic cell mutation.

Administration, Inhalation↗