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Something in the water? A health impact assessment of disinfection by-products in New Zealand.

Disinfection by-products (DBP) are a large group of halogenated chemicals formed by the reaction of disinfectant agents with naturally-occurring organic substances in water. Numerous studies have found associations between DBP and some cancers and adverse reproductive outcomes. For both cancer and birth defects the relative risk associated with exposure to DBP is about 1.5. About 66% of New Zealanders, or 2.4 million people, use chlorinated water supplies and are exposed to DBP. New Zealand's unique combination of flora, climate and geology will create unique mixtures of DBP but little detailed information is available on the level or composition of DBP in New Zealand. The population attributable risk per cent, for cancers and birth defects in New Zealand, is about 25%. In other words, a quarter of all bladder, colon and rectal cancers and birth defects may be preventable by reducing DBP exposure. This is equal to 329 preventable cancer deaths in 1995 and 94 preventable birth defects in 1996. DBP exposure can be reduced without compromising microbiological safety of water supplies. The health effects of DBPs must be weighed against the cost of DBP reduction and not against the potential water borne disease prevented by disinfection. Some aspects of New Zealand's water supplies and population provide a unique opportunity to undertake research. Further research is needed on the occurrence of DBPs and their health consequences in order to undertake a properly informed risk assessment.

Abnormalities, Drug-Induced↗

The liver-enriched transcription factor D-site-binding protein activates the promoter of the phosphoenolpyruvate carboxykinase gene in hepatoma cells.

It has been previously demonstrated that the CCAAT/enhancer-binding protein (C/EBP) trans-activates the gene coding for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) and binds to several sites along the promoter. The additional observations that C/EBP is expressed in liver and follows the same developmental profile as PEPCK suggests that C/EBP plays an important role in the regulation of PEPCK gene expression. However, since C/EBP is expressed at high levels in lung, a tissue in which PEPCK is not expressed, it appears that other mechanisms are involved to provide PEPCK with high level expression in liver. We now show that the albumin promoter D-site-binding protein (DBP), a transcription factor whose expression is limited to the liver, is also able to trans-activate the PEPCK promoter through sequence-specific binding. Both recombinant DBP and C/EBP bind with highest affinity to regions located at positions -85 and -245 in the promoter, but display differences in their binding properties at other sites. Using eukaryotic expression vectors for both C/EBP and DBP, we found that with 5'-deletion mutants of the PEPCK promoter, both C/EBP and DBP exerted their effects through similar regions of the promoter. However, the use of internal deletion mutants of the promoter identified distinct differences in the mechanism of activation by C/EBP and DBP. In particular, a region of the promoter between positions -86 and -117 significantly attenuated the level of trans-activation by DBP, but not by C/EBP. Evidence presented also supports a model whereby the relative ratios of C/EBP and DBP in the cell fine-tune the expression of the PEPCK gene. These results demonstrate that DBP and C/EBP, while having similar DNA binding specificities, have distinct functional differences in the context of the PEPCK promoter. These differences, along with the developmental profiles of C/EBP and DBP, may provide a mechanistic explanation for the liver-specific as well as the developmental profile of PEPCK gene expression.

Binding Sites↗

[Effect of dibutyl phthalate on the biochemical enzymes and lipid peroxidation in rat testes].

OBJECTIVE: To explore the effect of dibutyl phthalate (DBP) on the biochemical enzymes and lipid peroxidation in rats. METHODS: Healthy 6-week old male Sprague-Dawley rats were randomly divided into 4 groups with 16 in each. DBP dissolved in peanut oil was administered by gavage at dosages of 0, 250, 500 and 1000 mg/(kg x d). After 2- and 4-week DBP exposure, 8 rats in each group were killed, with certain organs selected and weighed. The activities of biochemical enzymes and glutathione peroxidase (GSH-Px) and the levels of glutathione (GSH) in the serum and testis homogenate were determined respectively. RESULTS: DBP induced a rise in the liver organ body weight ratio, but a fall in the testis organ body weight ratio, and it was significant in the highest exposure group compared with the control after either 2-week or 4-week treatment (P < 0.01). After 2-week DBP exposure, GSHPx activities in the serum and GSH levels in the testis homogenate showed a decreasing tendency, but GSHPx activities increased markedly in the testis homogenate (P < 0.05). After 4-week DBP exposure, while alkaline phosphatase (ALP) activities in the serum revealed an increasing tendency, sorbitol dehydrogenase (SDH) activities were inhibited significantly in both the serum and the testis homogenate at the dosage of 1000 mg/(kg x d) compared with the control group (P < 0.01). Furthermore, GSH contents in the serum were also affected at this dose (P < 0.05). CONCLUSION: The results indicate that DBP administration strongly affects the liver and the testis organ body weight ratios. Lipid peroxidation is one possible toxic mechanism caused by DBP. SDH may be one of the most sensitive toxic indices when exposed to DBP.

Alkaline Phosphatase↗

Salt sensitivity of blood pressure in patients with primary hypertension.

Objective measures of blood pressure (BP) sensitivity to 72-h salt depletion were evaluated. Salt sensitivity is defined as a measurable decrease of diastolic BP (DBP) after depletion. Changes in office auscultatory and oscillometric DBP were compared with oscillometric ambulatory DBP. In 35 women and men with mild hypertension, 24-h ambulatory DBP; sodium, potassium, albumin, and creatinine in 24-h urine; serum-creatinine; and body weight were measured before and at the end of the salt-free period. The oscillometric method detected larger and more uniform decreases in DBP compared to the auscultatory method. The salt depletion-induced changes in auscultatory DBP but not in ambulatory DBP were positively related to its baseline level. The salt sensitivity was positively related to the age and negatively related to the number of hypertensive symptoms. It was not related to body mass index and body weight decrease after salt depletion. The changes in ambulatory DBP were correlated to changes in office DBP (r = 0.46 for the auscultatory method; r = 0.58 for the oscillometric method). In only half the cases, the direction and size of pressure changes were reflected similarly in all three methods. Although the correlation between the methods points to the biological soundness of the salt sensitivity concept, the individual classification is prone to variation.

Adult↗

Seasonal differences in serum vitamin D binding protein in exclusively breast-fed infants: negative relationship to sunshine exposure and 25-hydroxyvitamin D.

Vitamin D binding protein (DBP) is the major carrier for vitamin D and its metabolites in serum. DBP increases in pregnancy and decreases in cirrhosis; no seasonal variation has been reported in adults. We observed significant seasonal differences in 41 exclusively breast-fed infants who were less than 6 months of age. Winter DBP concentrations exceeded summer DBP concentrations: 398 +/- 22 versus 297 +/- 20 micrograms/ml (mean +/- SEM). The mean concentration for spring and fall was 329 +/- 25 micrograms/ml. Maternal DBP concentrations did not differ by season. A sunshine exposure score, previously verified, was used to document time and body surface exposed to the sun. DBP was inversely related to sun exposure (r = -0.46, p = 0.005). Infant DBP was significantly and negatively correlated with 25-hydroxyvitamin D concentrations (r = - 0.38, p = 0.02). We speculate that serum DBP fluctuations are a response to varying vitamin D needs: increased serum DBP occurs in low vitamin D status to maximize uptake of vitamin D from skin.

Breast Feeding↗

The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats.

Osteopetrosis is a heterogeneous group of bone disorders characterized by the failure of osteoclasts to resorb bone and by several immunological defects including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF-1) and vitamin D-binding protein-macrophage activating factor (DBP-MAF) were used in the present study to evaluate their effects on the peritoneal population of cells and on cells within the bone marrow microenvironment in normal and incisors absent (ia) osteopetrotic rats. Previous studies in this laboratory have demonstrated that administration of DBP-MAF to newborn ia animals results in a substantial increase in bone marrow cavity size due to upregulated osteoclast function. To study the effects of these compounds on the macrophage/osteoclast precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to newborn ia and normal littermate animals. Both the normal and mutant phenotypes responded similarly when treated with these compounds. Rats exhibited a profound shift toward the macrophage lineage from the neutrophil lineage when compared with vehicle-treated control animals after treatment with these compounds. In the in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal cavity were then enumerated. The in vitro study consisted of cells isolated from the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF, or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at the expense of neutrophil numbers could be seen in both the in vivo and in vitro experiments. The macrophage/osteoclast and neutrophil lineages have a common precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the addition of CSF-1, the GM-CFC precursor may be induced into the macrophage/osteoclast lineage rather than the granulocyte lineage. This increased pool of cells in the macrophage/osteoclast lineage can be functionally upregulated with the subsequent addition of DBP-MAF to perform the activities of phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did not support colony development as in CSF-1 or the combination treatment. The recruitment and activation of cells into the macrophage/ osteoclast lineage may help to correct the bone and immune defects found in diseases demonstrating a significant lack of myeloid cells, as well as neutrophilia disorders and the disease, osteopetrosis.

Animals↗

Transport of vitamin D metabolites.

Vitamin D and its metabolites are bound to an alpha globulin (DBP) in human serum. This carrier protein binds 25-OHD and 24,25(OH)2D with higher affinity than vitamin D or 1,25(OH)2D, but the binding is highly specific for the vitamin D structure. The carrier mechanism appears to be unique in that it is a high affinity and high capacity system, capable of binding as much as 120,000 IU of biological activity per liter of plasma. DBP is apparently identical to group-specific component, and a DBP-deficient state has not been identified among approximately 75,000 human sera examined thus far. The liver appears to be the site for synthesis of DBP, and serum DBP levels are increased during pregnancy and during estrogen-progesterone therapy. However, in a variety of disorders of mineral homeostasis, serum DBP levels are normal. Two tissue binding proteins for vitamin D metabolites have been identified. One protein, sedimenting at 5-6S, has been found in all nucleated tissues, and exhibits a ligand preference similar to DBP. This tissue binding protein appears to be a complex of serum DBP with a tissue protein which is heat-labile, and which shows no capacity for binding vitamin D sterols. The physiologic role, if any, for this complex of serum DBP and tissue protein is not presently understood. The other tissue binding component is a 3-4S protein found only in recognized target tissues, and which shows a high binding affinity and specificity for 1,25(OH)2 D. It appears to be the receptor in the receptor-1,25(OH)2D migration to the nucleus, leading to the biosynthesis of mRNA which codes for products which affect calcium and phosphorus transport in target tissues.

Adult↗

Prognostic value of systolic and diastolic blood pressure in treated hypertensive men.

BACKGROUND: The aim of this study was to assess the cardiovascular risk in hypertensive subjects according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels. METHODS: The study sample consisted of 4714 hypertensive men, treated by their physician, who had a standard health checkup at the d'Investigations Préventives et Cliniques Center, Paris, France, between 1972 and 1988. Cardiovascular disease (CVD) and coronary heart disease (CHD) mortality were assessed for a mean period of 14 years. RESULTS: Among treated subjects, 85.5% presented uncontrolled values for SBP (> or = 40 mm Hg) and/or DBP (> or = 90 mm Hg). After adjustment for age and associated risk factors, these subjects presented an increased risk for CVD mortality (risk ratio [RR], 1.66; 95% confidence interval [CI], 1.04-2.64) and for CHD mortality (RR, 2.35; 95% CI, 1.03-5.35) compared with controlled subjects. After adjustment for age, associated risk factors, and DBP, and compared with subjects with SBP under 140 mm Hg, the RR for CVD mortality was 1.81 (95% CI, 1.04-3.13) in subjects with SBP between 140 and 160 mm Hg and 1.94 (95% CI, 1.10-3.43) in subjects with SBP over 160 mm Hg. By contrast, after adjustment for SBP levels, CVD risk was not associated with DBP. Compared with subjects with DBP under 90 mm Hg, RR for CVD mortality was 1.17 (95% CI, 0.80-1.70) in subjects with DBP between 90 and 99 mm Hg and 1.03 (95% CI, 0.67-1.56) in subjects with DBP over 100 mm Hg. Similar results were observed for CHD mortality. CONCLUSIONS: In hypertensive men treated in clinical practice, SBP is a good predictor of CVD and CHD risk. Diastolic blood pressure, which remains the main criterion used by most physicians to determine drug efficacy, appears to be of little value in determining cardiovascular risk. Evaluation of risk in treated individuals should take SBP rather than DBP values into account.

Adult↗

Development of novel poly(ethylene glycol)-based vehicles for gene delivery.

The purpose of this research was to develop and characterize a gene delivery vehicle with a poly(ethylene glycol) (PEG) backbone with the aim of overcoming limitations, such as cytotoxicity and rapid clearance, associated with current commonly used non-viral carriers. PEG was functionalized with DNA-binding peptides (DBPs) to make a vehicle (DBP-PEG) capable of condensing DNA. Complexes of plasmid DNA and DBP-PEG were formed and characterized by measuring particle size, zeta potential, and transfection efficiency as a function of N:P charge ratios (DBP-PEG amino groups:DNA phosphate). Dynamic light scattering showed that DBP-PEG was able to condense DNA efficiently resulting in a population of particles in the range of 250-300 nm. Neutral or slightly positive zeta potentials were measured for charge ratios of 3.5:1 and greater. DBP-PEG/DNA complexes, made with plasmids encoding the green fluorescent protein (GFP) and beta-Galactosidase (beta-Gal) genes, were used to transfect Chinese hamster ovary (CHO) cells. DBP-PEG/DNA was capable of transfecting cells and maximum transfection efficiency was observed for N:P ratios from 4:1 to 5:1, corresponding to zeta potentials from -4 to +1.6 mV. The effect of the DBP-PEG vehicle on cell viability was assayed. DBP-PEG was associated with a higher percentage of viable cells ( approximately 95%) than either polyethylenimine (PEI) or poly-L-lysine (PLL), and with transfection efficiency greater than PLL, but with somewhat lower than PEI. The results of this work demonstrate that PEG can be used as the backbone for gene delivery vehicles.

Gene Transfer Techniques↗

Multiple functions of the adenovirus DNA-binding protein are required for efficient viral DNA synthesis.

Mutational analysis within the amino-terminal (N-t) domain of the adenovirus DNA-binding protein (DBP) defined a region (aa 2-38) important for DBP function. Several viruses carrying lesions in this region of DBP showed reduced accumulation of viral DNA and infectious virions. Characterization of one of these mutants, H5in800, indicated that the N-t domain affects viral DNA synthesis in vivo. The reduction in DNA synthesis was not due to a change in the amount or nuclear location of the H5in800 DBP. Expression of other early genes in H5in800-infected cells was similar to that seen in wild-type Ad5-infected cells, suggesting that the depression of DNA synthesis was not due to disruption of DBP's role in early gene expression. The H5in800 and wild-type DBP also had comparable affinities for single-stranded DNA and functioned with similar efficiencies in two DNA elongation assays. Prior studies have shown that the carboxyl-terminal (C-t) domain of DBP was responsible for these two activities. Together these results suggest that DBP has at least two separable functions in viral DNA replication in vivo and that both domains of the protein are necessary for full activity. The intragenic complementation between the N-t mutant H5in800 and the C-t mutant H5in804 supports this model.

Adenoviruses, Human↗

Phosphorylation of the adenovirus DNA-binding protein and epitope mapping of monoclonal antibodies against it.

To facilitate structure/function studies of the adenovirus type 2 or 5 single-stranded DNA binding protein (DBP), the epitopes of five anti-DBP monoclonal antibodies were mapped. Antibodies 37-3, 38-2, and B6 mapped between DBP residues 131-174 which corresponds to the host-range or hinge region of the molecule. The epitopes for antibodies 16-5 and 18-9 mapped between residues 58-81, and included a phosphorylated serine at position 70. Using antibodies 16-5 or 18-9 as analytical reagents, approximately 1/2 of the DBP molecules present at late times in infected HeLa cells were found to be phosphorylated at serine 70. A similar pattern of serine 70 phosphorylation was observed in productively and abortively infected monkey cells as well as in an E2A-transformed, DBP expressing cell lines. This study also reports the preliminary identification of two new phosphorylation sites on Ad2 DBP at serines 160 and 161 (corresponding to serine 161 on Ad5 DBP). No differences were observed in the phosphorylation of serine 160/161 in DBP isolated from infected HeLa cells or from productively and abortively infected monkey cells. Therefore, phosphorylation of these sites cannot account for the block to wild-type adenovirus growth in monkey cells.

Adenovirus E2 Proteins↗

DNA-binding proteins in the sera of patients with malignant melanoma.

Sera of patients with various malignancies are known to contain DNA-binding proteins (DBP) which are not present in sera of normal individuals. In this paper sera of patients with malignant melanoma (MM) were examined as to whether characteristic DBP are present, too. DBP are isolated by DNA-affinity chromatography and represent 0.5-0.9% of all serum proteins. After separation of the DBP by SDS slab gel electrophoresis no typical DBP is detectable in sera of MM-patients. However, quantitative differences are found in sera of patients in the clinical stages I-III and/or tumor level 3-5: 1. All 9 sera of patients who had clinical signs of MM contain more DBP with molecular weight (mw) of 20,000-24,000 dalton than control sera. However, these DBP are only increased in 30% of the 22 sera from MM-patients who had clinical signs for 13-73 months after tumor excision. 2. All sera of the 10 MM-patients of whom sera were drawn twice after tumor excision at an interval of 7-46 months without clinical signs, showed a reduction of DBP with mw 30,000, 68,000, and 165,000.

Adult↗

Acute effects of 2-bromopropane and 1,2-dibromopropane on hepatotoxic and immunotoxic parameters in female BALB/c mice.

In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice. The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights of the spleen and thymus weights and decreased the number of splenic cells. In addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs. Meanwhile, only the antibody response was significantly suppressed by treatment with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1,2-DBP on the hepatotoxic parameters were compared in female BALB/c mice. When mice were treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the activities of serum alanine aminotransferase and aspartate aminotransferase elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200 also contributes to the immnunotoxicity, although 2-BP is a major component.

Alanine Transaminase↗

Identification of epitope on DNA-binding protein expressed in insect cell infected by baculovirus.

DNA-binding protein (DBP) is an early gene product produced during viral replication. Polyclonal anti-DBP was produced using rabbit by intradermal injections of Escherichia coli-expressed purified recombinant DBP. Prepared anti-DBP completely blocked the replication of baculovirus in insect cells. The anti-DBP binding to DBP was confirmed by both Western blotting with Tn-5B1-4 insect cell lysates as well as immunostained baculovirus-infected Tn-5B1-4 insect cells. To determine the anti-DBP epitope 12 peptides were synthesized and their specific-binding activities were measured using ELISA. Based on specific-binding activity against anti-DBP the epitope was predicted to be between amino acid residues 248-265 (QRMSVEDFDRLFEMDKID). Especially from 18 amino acid residues it was further to be narrowed between amino acid residues 260-265 (EMDKID) which showed a critical role in specific-binding activity.

Animals↗

The uptake and metabolism of 25-hydroxyvitamin D3 and vitamin D binding protein by cultured porcine kidney cells (LLC-PK1).

1. Uptake of 3H-25OHD3, 3H-25OHD3-DBP, 125I-holo-DBP and 125I-apo-DBP by LLC-PK1 cells was linearly related to the concentration of each in the culture media. The presence of DBP in the medium significantly reduced the amount of 3H-25OHD3 taken up by cells. 2. Free 25OHD3 and 25OHD3 bound to DBP were both metabolized by the cells to 24,25(OH)2D3 and an unidentified product of apparent lower polarity than 25OHD3. 3. A significant amount of DBP taken up by the LLC-PK1 cells was metabolized to a TCA-soluble form. 4. Uptake of DBP was similar to horseradish peroxidase, but higher than inulin, indicative of a non-specific endocytic mechanism with an adsorptive component. 5. It is suggested that both free circulating 25OHD3 and that derived from lysosomal degradation of 25OHD3-DBP are available for hydroxylation by the kidney.

Animals↗

Structure and function of DNA binding proteins from revertants of adenovirus type 5 mutants with a temperature-sensitive DNA replication.

H5ts107 and H5ts125 are two adenoviruses type 5 (Ad5) mutants with a temperature-sensitive DNA replication. Both mutants contain an altered gene encoding the DNA binding protein (DBP). We have established by nucleotide sequence analysis that both mutants carry exactly the same mutation in the DBP gene resulting in the substitution of a proline residue at position 413 in the wild-type DBP amino acid sequence (529 amino acid residues long) by a serine residue. Revertants of H5ts107 and H5ts125, which are temperature independent in plaque efficiency and growth in HeLa cells at 32 degrees and 39 degrees, were characterized by nucleotide sequence analysis of their DBP genes. Four types of revertants could be distinguished: revertants with the wild-type DBP amino acid sequence (type I) and, revertants carrying, in addition to the original H5ts107/H5ts125 mutation at position 413, intragenic second site mutations at position 508 histidine leads to tyrosine (type II), at position 352 glycine leads to aspartic acid (type III), and at position 347 alanine leads to proline (type IV), respectively. All intragenic second site mutations are located, together with the H5ts107/H5ts125 mutation, in the C-terminal 45-kD fragment of the adenovirus DBP molecule. This provides further evidence that this part of the DBP molecule plays an important role in viral DNA replication. Phenotypic characterization of the revertants (J.C. Nicolas, F. Suarez, A.J. Levine, and M. Girard (1981), Virology 108, 521-524; (J.C. Nicolas, D. Ingrand, P. Sarnow, and A.J. Levine (1982), Virology 122, 481-485) has shown that the second site mutations reveal additional functional domains in the DBP molecule.

Adenoviruses, Human↗

Effects of preservation on the osteoinductive capacity of demineralized bone powder allografts.

Demineralized bone powder (DBP) has repeatedly been shown to serve as an osteoinductive material. The aim of this study was to investigate the effects of different methods of storage of DBP on its osteoinductive property. Forty-five Long Evan rats were used in this study. Twenty rats were used as donors; the diaphyses of their femoral bones were used for the preparation of DBP. The DBP was divided into four portions that were either lyophilized or frozen at -70 degrees C, -4 degrees C, or kept at room temperature (25 degrees C). All samples were stored under the specified condition for six months. At the time of implantation, fresh DBP was prepared and used as a control. Twenty-five rats were divided equally into five groups. Each group received an implant of either one of the differently preserved and stored samples of DBP or fresh DBP. The animals were killed 60 days following implantation. The implants were excised and processed to obtain 5 micron thick decalcified sections and 3 micron thick undecalcified sections. Semicomputerized histomorphometry was used for the quantification of the newly-formed bone in each implant. Newly-formed bone was detected in all experimental and control groups and there were no statistically significant differences between the various groups. It was concluded that DBP retains its osteoinductivity after lyophilization or preservation at -70 degrees C, -4 degrees C, and 25 degrees C for a period of up to six months, and that the different methods of preservation did not significantly affect the amount of the induced newly-formed bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vitamin D binding protein: genomic structure, functional domains, and mRNA expression in tissues.

The vitamin D binding protein (DBP), alternatively known as Gc-globulin, is a member of the albumin (ALB) and alpha-fetoprotein (AFP) gene family. The rat DBP gene is expressed at high levels in liver and at moderate levels in kidney, testis, abdominal fat, and yolk sac. Very low levels of DBP as well as ALB and AFP transcripts can be detected in all other tissues studied by the reverse transcriptase/polymerase chain reaction technique. During development, liver DBP gene transcripts are detectable at 14 days of gestation and levels rise gradually until adulthood in parallel with ALB. DBP present on the surface of U937 monocyte-derived cells is acquired from serum, suggesting cell surface binding sites for DBP. The rat DBP gene has been cloned and characterized. It spans 35 kb and contains 13 exons and 12 introns. The DBP gene contains two fewer exons than the ALB or AFP genes, accounting for the shortest size of its mRNA and protein product. Its 5'-flanking region contains a high degree of structural similarity to both ALB and AFP promoters.

Amino Acid Sequence↗