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At least 595 records · Page 33Linked to original sources
PubMed1993

Dissimilar expression patterns for the extracellular matrix proteins osteopontin (OPN) and collagen type I in dental tissues and alveolar bone of the neonatal rat.

Osteopontin (OPN) is a phosphorylated, sialic acid containing glycoprotein that can be extracted from the mineralized extracellular matrix of bone. In the present study we determined the expression patterns of OPN in dental tissues and alveolar bone of 1-3 day old (neonatal) rats by means of 1) immunohistochemistry, 2) Northern blotting and 3) in situ hybridization. We compared these patterns with those of type I collagen. We localized collagen type I expression in osteoblasts adjacent to alveolar bone and in odontoblasts lining predentin/dentin, but not in the epithelial ameloblasts. For OPN, we observed a weak antigenicity in predentin. Although generally no cellular immunostaining was found, very occasionally a minor immunoreactivity was detected in a small number of pre-mineralizing incisor odontoblasts. On the mRNA level, however, no OPN transcripts could be detected in odontoblasts, either by in situ or by Northern hybridization analyses. Also the odontoblasts of the bone-like dentin (osteodentin) region in the tip of incisors were negative for OPN. In contrast, however, osteoblasts of alveolar bone showed strong positive signals with all three techniques, confirming the sensitivity and specificity of the detection methods. From the data obtained in this study, it can be concluded that during early stages of dentinogenesis OPN presumably is not expressed in developing rat tooth germs. The weak immunostaining observed sporadically in some young odontoblasts is probably due to resorption of OPN of non-dental origin entrapped in the predentin.

Alveolar Process↗
PubMed1993

Transient expression of type III collagen by odontoblasts: developmental changes in the distribution of pro-alpha 1(III) and pro-alpha 1(I) collagen mRNAs in dental tissues.

The expression of pro-alpha 1(III) and pro-alpha 1(I) collagen mRNAs in mouse and human dental tissues during tooth development and after its completion was analyzed by in situ hybridization, with use of [35S]-labeled RNA probes. The expression of pro-alpha 1(III) mRNA was also compared to that of the protein product, as localized by immunostaining with polyclonal antibodies to type III collagen and the N-terminal propeptide of type III procollagen. Contrary to many previous reports, our results suggest that odontoblasts express type III collagen. While pro-alpha 1(III) transcripts were less intensely expressed in odontoblasts than pro-alpha 1(I) transcripts, the amounts of both mRNAs increased in odontoblasts with progressing dentin formation, and decreased toward its completion. In contrast to pro-alpha 1(III) mRNA, pro-alpha 1(I) mRNA was still detectable in odontoblasts of fully developed teeth. Type III collagen immunoreactivity was observed in the early predentin, and again in predentin toward the completion of dentinogenesis, when mRNA was no longer detected. Also in the pulp, the protein product, unlike pro-alpha 1(III) mRNA, was relatively strongly expressed. Hence, these immunostaining patterns were inversely related to the expression of pro-alpha 1(III) mRNA, suggesting accumulation of the protein. The mesenchymal cells, when condensed in the region of the future mandibular bone, expressed pro-alpha 1(III) mRNA intensely, whereas osteoblasts expressed pro-alpha 1(I) but not pro-alpha 1(III) transcripts strongly. Cell type- and developmental stage-related differences in the expression of the two mRNAs suggest that type I/type III collagen ratio influences the structure of dental tissues.

Aging↗
PubMed1995

Intermediate cementum. Development, structure, composition, and potential functions.

In the roots and root analogs of mammalian teeth a narrow zone of highly calcified tissue occupies the junction between cementum and dentin. This zone is referred to as "intermediate cementum," despite evidence that it is not a product of cementogenesis (or of dentinogenesis). Studies conducted on teeth of human and nonhuman primates indicate that the intermediate cementum layer contains enamel matrix proteins and is likely a product of Hertwig's epithelial root sheath. The available evidence regarding the development (origin), structure, and composition of intermediate cementum is reviewed, and the potential functions of this layer are assessed to include a possible role in wound healing.

Animals↗
PubMed2002

Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth.

Biochemical investigations in rodents have shown that numerous mineralized matrix proteins share expression in bone, dentin, and cementum. Little information is available regarding the expression pattern of these proteins in human tissues, particularly during tooth formation. The aim of this study was to identify the expression pattern of the two major noncollagenous proteins of bone and dentin, osteocalcin (OC) and osteonectin (ON), in comparison to the dentin-specific protein, dentin sialophosphoprotein (DSPP). Mandibles from fetuses (5-26 weeks), neonate autopsies, forming teeth from 10-12-year-old patients, third molars extracted for orthodontic reasons, and bone tumors were collected with approval from the National Ethics Committee. Human OC, ON, and DSPP mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR) in fetal mandibles (5-11 weeks) and in primary cell cultures of dental pulp. In addition, OC, ON, and DSPP proteins were localized in forming human mineralized tissues using immunohistochemistry. In vivo, DSPP expression was associated with tooth terminal epithelial-mesenchymal interaction events, amelogenesis and dentinogenesis. Transient DSPP expression was seen in the presecretory ameloblasts with continuous expression in the odontoblasts. In contrast, both osteoblasts and odontoblasts showed a temporal gap between OC and ON expression in early development. ON was expressed in the initial stages of cytodifferentiation, whereas OC was expressed only during the later stages, especially in the teeth. At the maturation stage of enamel formation, both proteins were detected in odontoblasts and their processes within the extracellular matrix. In contrast to bone, OC was not localized extracellularly within the collagen-rich dentin matrix (predentin or intertubular dentin), but was found in the mature enamel. ON was present mostly in the nonmineralized predentin. These results demonstrate for the first time that both OC and ON are produced by human odontoblasts and determine the expression pattern of DSPP in human teeth, and suggest that OC and ON move inside the canalicule via odontoblast cell processes becoming localized to specific extracellular compartments during dentin and enamel formation. These distinct extracellular patterns may be related to the nature of DSPP, OC, and ON interactions with other matrix-specific macromolecules (i.e., amelogenin, dentin matrix protein-1) and/or to the polarized organization of odontoblast secretion as compared with osteoblasts.

Adult↗
PubMed2000

Ultrastructural localisation of TGF-beta exposure in dentine by chemical treatment.

Transforming growth factor-beta (TGF-beta) sequestered in dentine matrix has an important role in dental tissue repair after injury and its exposure at sites of injury may stimulate tertiary dentinogenesis. This study aimed to investigate the expression of TGF-beta isoforms in mature human dentine matrix and the ability of chemical treatments to expose TGF-beta on the cut surface of dentine using gold immunolabelling and subsequent scanning electron microscopy examination. TGF-beta1 was the only isoform that could be detected in human dentine and the nature of the chemical treatment of the tissue influenced its detection. EDTA treatment provided good exposure of TGF-beta1 on the dentine surface, whilst citric acid and sodium hypochlorite treatments revealed lesser amounts of this isoform. Only minimal staining for TGF-beta1 was observed in samples treated with phosphate-buffered saline. TGF-beta2 and -beta3 could not be detected in the specimens with any of the treatments. This study suggests that TGF-beta1 is the only TGF-beta isoform expressed by human odontoblasts to be sequestered in dentine implying that differences in isoform-extracellular matrix interactions may exist. Information on chemical treatment of tissue specimens for immunostaining may provide a useful basis for selection of tissue preparation techniques for clinical restorative treatment procedures to facilitate TGF-beta mediated reparative processes at sites of dental injury.

Citric Acid↗
PubMed2001

BMP-7 gene transfer to inflamed ferret dental pulps.

In vivo and ex vivo gene transfer are being developed for localized skeletal regeneration. These strategies for tissue regeneration were tested in an adult ferret model of vital pulp therapy. In this model a reversible pulpitis was induced first. Then after 3 d, the pulps were directly infected with recombinant virus or implanted with ex vivo transduced autologous dermal fibroblasts. The genome of the recombinant adenovirus contained a full-length cDNA encoding mouse bone morphogenetic protein (BMP)-7 (AdBMP7) or bacterial beta-galactosidase cDNA (AdlacZ). The BMP-7, but not lacZ, ex vivo transduced dermal fibroblasts induced reparative dentinogenesis with apparent regeneration of the dentin-pulp complex. In vivo infection with AdBMP-7 failed to produce reparative dentin in all cases. E. vivo gene transfer of BMP-7 may be an effective method for inducing dentin regeneration in teeth with reversible pulpitis.

Adenoviridae↗
PubMed1999

Morphology of dental enamel and dentine-enamel junction in osteogenesis imperfecta.

OBJECTIVES: The aim of this study was to examine the morphology of primary and permanent human enamel, and the dentine-enamel junction, in individuals with osteogenesis imperfecta (OI) type I, III and IV in undecalcified sections using polarized light microscopy, microradiography and scanning electron microscopy (SEM), and to relate the findings to the type of OI. SAMPLE AND METHODS: Extracted or exfoliated teeth from 15 patients representing the OI types I, III and IV (12 primary teeth from seven patients, and 11 permanent teeth from eight patients). Ten primary and nine permanent teeth from normal healthy patients served as controls. The teeth were serially cut longitudinally in a bucco-lingual direction and contact microradiographs were made. The sections were examined in polarized light. Sections of primary and permanent teeth were examined by means of SEM. RESULTS: This study shows that the permanent enamel from patients with OI exhibits few structural changes. No relationships were found between enamel morphology and the types of OI (I, III, IV). Primary enamel appeared to be slightly more irregularly mineralized, especially in cases with the additional diagnosis dentinogenesis imperfecta. The major findings were deviations in association with the dentine-enamel junction, and locally a lower degree of mineralization. CONCLUSIONS: The mesodermal disease OI might also be manifested in ectodermal enamel, probably because of suboptimal mesenchymal-ectodermal interactions during amelogenesis.

Dental Enamel↗
PubMed1996

Multiexon deletions in the type I collagen COL1A2 gene in osteogenesis imperfecta type IB. Molecules containing the shortened alpha2(I) chains show differential incorporation into the bone and skin extracellular matrix.

Osteogenesis imperfecta (OI) type IB is a rare subset of the mildest form of OI, clinically characterized by moderate bone fragility, blue sclera, and dentinogenesis imperfecta. Cultured skin fibroblasts from two unrelated individuals (OI-197 and OI-165) with the typical features of OI type IB produced shortened alpha2(I) chains. Reverse transcription-polymerase chain reaction of the alpha2(I)-cDNA revealed deletions in the triple helical domain of 5 exons (exons 7-11) in OI-197, and 8 exons (exons 10-17) in OI-165. This exon skipping was caused by genomic deletions in one allele of COL1A2 with the breakpoints located in introns 6 and 11 in OI-197, and introns 9 and 17 in OI-165. The secretion and deposition of the mutant collagen into the matrix was measured in vitro in cultures of skin fibroblasts and bone osteoblasts, grown in the presence of ascorbic acid to induce collagen matrix formation and maturation, as well as in collagen extracts from skin and bone. The secretion of mutant collagen was impaired and long term cultures of fibroblasts showed that the mutant collagen was not incorporated into the mature collagenous matrix produced in vitro by skin fibroblasts from both patients. Likewise, the shortened alpha2(I) chain was not demonstrable in skin extracts. In contrast, bone extracts from OI-197 showed the presence of the mutant collagen. This incorporation of the abnormal collagen into the mature matrix was also demonstrated in long term cultures of the patient's osteoblasts. The deposition of the mutant collagen by bone osteoblasts but not by skin fibroblasts demonstrates a tissue specificity in the incorporation of mutant collagen into the matrix which may explain the primary involvement of bone and not skin in these patients.

Adolescent↗
PubMed1997

Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed from a single transcript coded by a gene on human chromosome 4. Dentin phosphoprotein DNA sequence determination.

Dentin is the major mineralized extracellular matrix of the tooth. The organic components of dentin consist of type I collagen (90%) with 10% noncollagenous proteins, which are also components of bone. Two dentin proteins, dentin sialoprotein and dentin phosphoprotein, have been shown to be tooth-specific being expressed mostly by odontoblast cells. In this study, we screened a mouse molar tooth library for dentin sialoprotein and dentin phosphoprotein cDNA clones. Analysis of the clones resulted in characterization of a 4420-nucleotide cDNA that contained a 940-amino acid open reading frame. The signal peptide and NH2-terminal sequence was 75% homologous to the cDNA sequence of rat dentin sialoprotein. The continued open reading frame, however, contained a RGD sequence followed by a region of repeated aspartic acid and serine residues. This portion of the protein codes for amino acid sequence consistent with that of dentin phosphoprotein. The noncoding region contains three potential polyadenylation signals, two of which were shown to be utilized. Northern blot analysis indicated the presence of two major transcripts of 4.4 and 2.2 kilobases in odontoblasts. Chromosomal mapping localized the gene to human chromosome 4. These data suggest that the previously identified dentin extracellular matrix proteins, dentin sialoprotein and dentin phosphoprotein, are expressed as a single cDNA transcript coding for a protein that is specifically cleaved into two smaller polypeptides with unique physical-chemical characteristics. Therefore, we propose that the gene be named dentin sialophosphoprotein. The location of the human dentin sialophosphoprotein gene on chromosome 4 suggests that this gene may be a strong candidate gene for the genetic disease dentinogenesis imperfecta type II.

Amino Acid Sequence↗
PubMed2003

Evidence for the proteolytic processing of dentin matrix protein 1. Identification and characterization of processed fragments and cleavage sites.

Full-length cDNA coding for dentin matrix protein 1 (DMP1) has been cloned and sequenced, but the corresponding complete protein has not been isolated. In searching for naturally occurring DMP1, we recently discovered that the extracellular matrix of bone contains fragments originating from DMP1. Shortened forms of DMP1, termed 37K and 57K fragments, were treated with alkaline phosphatase and then digested with trypsin. The resultant peptides were purified by a two-dimensional method: size exclusion followed by reversed-phase high performance liquid chromatography. Purified peptides were sequenced by Edman degradation and mass spectrometry, and the sequences compared with the DMP1 sequence predicted from cDNA. Extensive sequencing of tryptic peptides revealed that the 37K fragments originated from the NH2-terminal region, and the 57K fragments were from the COOH-terminal part of DMP1. Phosphate analysis indicated that the 37K fragments contained 12 phosphates, and the 57K fragments had 41. From 37K fragments, two peptides lacked a COOH-terminal lysine or arginine; instead they ended at Phe173 and Ser180 and were thus COOH termini of 37K fragments. Two peptides were from the NH2 termini of 57K fragments, starting at Asp218 and Asp222. These findings indicated that DMP1 is proteolytically cleaved at four bonds, Phe173-Asp174, Ser180-Asp181, Ser217-Asp218, and Gln221-Asp222, forming eight fragments. The uniformity of cleavages at the NH2-terminal peptide bonds of aspartyl residues suggests that a single proteinase is involved. Based on its reported specificity, we hypothesize that these scissions are catalyzed by PHEX protein. We envision that the proteolytic processing of DMP1 plays a crucial role during osteogenesis and dentinogenesis.

Alkaline Phosphatase↗
PubMed2003

Laminin alpha2 is essential for odontoblast differentiation regulating dentin sialoprotein expression.

Laminin alpha2 is subunit of laminin-2 (alpha2beta1gamma1), which is a major component of the muscle basement membrane. Although the laminin alpha2 chain is expressed in the early stage of dental mesenchyme development and localized in the tooth germ basement membrane, its expression pattern in the late stage of tooth germ development and molecular roles are not clearly understood. We analyzed the role of laminin alpha2 in tooth development by using targeted mice with a disrupted lama2 gene. Laminin alpha2 is expressed in dental mesenchymal cells, especially in odontoblasts and during the maturation stage of ameloblasts, but not in the pre-secretory or secretory stages of ameloblasts. Lama2 mutant mice have thin dentin and a widely opened dentinal tube, as compared with wild-type and heterozygote mice, which is similar to the phenotype of dentinogenesis imperfecta. During dentin formation, the expression of dentin sialoprotein, a marker of odontoblast differentiation, was found to be decreased in odontoblasts from mutant mice. Furthermore, in primary cultures of dental mesenchymal cells, dentin matrix protein, and dentin sialophosphoprotein, mRNA expression was increased in laminin-2 coated dishes but not in those coated with other matrices, fibronectin, or type I collagen. Our results suggest that laminin alpha2 is essential for odontoblast differentiation and regulates the expression of dentin matrix proteins.

Animals↗
PubMed2004

Dmp1-deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype.

Understanding the molecular mechanisms by which cartilage formation is regulated is essential toward understanding the physiology of both embryonic bone development and postnatal bone growth. Although much is known about growth factor signaling in cartilage formation, the regulatory role of noncollagenous matrix proteins in this process are still largely unknown. In the present studies, we present evidence for a critical role of DMP1 (dentin matrix protein 1) in postnatal chondrogenesis. The Dmp1 gene was originally identified from a rat incisor cDNA library and has been shown to play an important role in late stage dentinogenesis. Whereas no apparent abnormalities were observed in prenatal bone development, Dmp1-deficient (Dmp1(-/-)) mice unexpectedly develop a severe defect in cartilage formation during postnatal chondrogenesis. Vertebrae and long bones in Dmp1-deficient (Dmp1(-/-)) mice are shorter and wider with delayed and malformed secondary ossification centers and an irregular and highly expanded growth plate, results of both a highly expanded proliferation and a highly expanded hypertrophic zone creating a phenotype resembling dwarfism with chondrodysplasia. This phenotype appears to be due to increased cell proliferation in the proliferating zone and reduced apoptosis in the hypertrophic zone. In addition, blood vessel invasion is impaired in the epiphyses of Dmp1(-/-) mice. These findings show that DMP1 is essential for normal postnatal chondrogenesis and subsequent osteogenesis.

Animals↗
PubMed2006

Dentin sialophosphoprotein is processed by MMP-2 and MMP-20 in vitro and in vivo.

Dentin sialophosphoprotein (DSPP) is a major secretory product of odontoblasts and is critical for proper tooth dentin formation. During dentinogenesis, DSPP is proteolytically cleaved into smaller subunits. These cleavages are proposed activation steps, and failure to make these cleavages is a potential cause of developmental tooth defects. We tested the hypothesis that dentin-resident matrix metalloproteinases catalyze the cleavages that process DSPP. We defined the exact DSPP cleavages that are catalyzed by proteases during crown formation by isolating DSPP-derived proteins from developing porcine molars and characterizing their N-terminal sequences and apparent size on SDS-PAGE and Western blots. The in vivo DSPP cleavage sites were on the N-terminal sides of Thr(200), Ser(330), Val(353), Leu(360), Ile(362), Ser(377), Ser(408), and Asp(458). The initial DSPP cleavage is between dentin glycoprotein (DGP) and dentin phosphoprotein (DPP), generating dentin sialoprotein (DSP)/DGP and DPP. Gelatin and casein zymograms identified MMP-2, MMP-20, and KLK4 in the dentin extracts. MMP-2 and MMP-20 were purified from over 150 g of porcine dentin powder and incubated with DSP-DGP and DPP. These enzymes show no activity in further cleaving DPP. MMP-20 cleaves DSP-DGP to generate DSP and DGP. MMP-20 also cleaves DSP at multiple sites, releasing N-terminal DSP cleavage products ranging in size from 25 to 38 kDa. MMP-2 makes multiple cleavages near the DSP C terminus, releasing larger forms of DGP, or "extended DGPs." Exact correspondence between DSPP cleavage sites that occur in vivo and those generated in vitro demonstrates that MMP-2 and MMP-20 process DSPP into smaller subunits in the dentin matrix during odontogenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Morphological classification of dental lesions induced by various antitumor drugs in mice.

To characterize and compare maxillary incisor lesions caused by various antitumor drugs, male BALB/c mice were given a single intravenous injection of an estimated 10% lethal dose (LD10)) of 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C (MMC), vinblastine sulfate (VBL). taxotere (TXR), irinotecan hydrochloride (CPT-11), DX-8951f, or cisplatin (CDDP). After 3, 5, 10, 15, and 60 days, the animals were sacrificed, and the maxillary incisors were examined microscopically. The dental lesions observed were classified into 4 different types on the basis of their morphological features. The lesion due to 5-FU was characterized by focal defects in the dentin, and this injury was reversible (transient dentin injury). ADR- or MMC-induced lesions were defined by abnormal structure of the apical aspect of the tooth and irregular odontogenesis, lasting for a long period (persistent apical injury). Treatment with VBL or TXR showed irregular enamel formation and abnormal dentinogenesis. Their targets were considered to be both immature and mature odontogenic cells (diffuse dental injury). Exposure to CPT-11, DX-8951f, or CDDP elicited minor reductions in a few precursor cells in the epithelial sheath on day 3, but no prominent dental abnormalities were seen thereafter (nontoxic injury). In conclusion, antitumor drugs can cause a variety of dental lesions that vary temporally and spatially, making histopathological examination of the maxillary incisor an important component of the safety assessment process for novel antitumor drugs.

Animals↗
PubMed2002

MEPE/OF45, a new dentin/bone matrix protein and candidate gene for dentin diseases mapping to chromosome 4q21.

Substantial progress has been made regarding the molecular etiology of the dentin diseases dentinogenesis imperfecta types II and III, and dentin dysplasia type II. Genetic linkage studies have identified the critical loci for these diseases on human chromosome 4q21. Located within an overlapping segment of these disease loci is a dentin/bone gene cluster that includes osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein, and a new gene MEPE also known as OF45, renamed osteoregulin. In this paper, we report the location of MEPE/OF45 in relationship to the other members of the dentin/bone gene cluster as well as the genomic organization of the human gene. For the first time, MEPE/OF45 expression was shown in dental tissue, in particular odontoblasts, by reverse-transcription polymerase chain reaction (RT-PCR) amplification and characterization of a partial mouse cDNA. Our data provide the first evidence that MEPE/OF45 is expressed during odontogenesis and should be considered as a candidate gene for dentin structural diseases mapping to human chromosome 4q21.

Animals↗
PubMed2004

Development of an odontoblast in vitro model to study dentin mineralization.

The aim of the present work was to characterize the odontoblastic proliferation, differentiation, and matrix mineralization in culture of the recently established M2H4 rat cell line. Proliferation was assessed by cell counts, differentiation by RT-PCR analysis, and mineralization by alizarin red staining, atomic absorption spectrometry, and FTIR microspectroscopy. The results showed that M2H4 cell behavior closely mimics in vivo odontoblast differentiation, with, in particular, temporally regulated expression of DMP-1 and DSPP. Moreover, the mineral phase formed by M2H4 cells was similar to that in dentin from rat incisors. Finally, because in mice, transforming growth factor (TGF)-beta1 over-expression in vivo leads to an hypomineralization similar to that observed in dentinogenesis imperfecta type II, effects of TGF-beta1 on mineralization in M2H4 cell culture were studied. Treatment with TGF-beta1 dramatically reduced mineralization, whereas positive control treatment with bone morphogenetic protein-4 enhanced it, suggesting that M2H4 cell line is a promising tool to explore the mineralization mechanisms in physiopathologic conditions.

Animals↗
PubMed1994

Localization of a gene for autosomal dominant amelogenesis imperfecta (ADAI) to chromosome 4q.

Amelogenesis imperfecta (AI), is an inherited odontological disease which affects the formation of enamel. We report a linkage analysis study performed on three Swedish families, where the affected members had an autosomal dominant variant of AI (ADAI) clinically characterized as local hypoplastic. Significant linkage to microsatellite markers on chromosome 4q were obtained. Recombinations localized the ADAI locus to a chromosome region which contains both a locus for the dental disorder dentinogenesis imperfecta and the albumin gene. Serum albumin has been suggested to play a role in enamel formation, and the albumin gene is therefore a candidate gene for this genetic disease.

Amelogenesis Imperfecta↗
PubMed2006

7,12-dimethylbenz[a]anthracene interferes with the development of cultured mouse mandibular molars.

Clinical studies suggest that maternal smoking during pregnancy can reduce the crown size of the child's teeth. Delayed dental age compared with chronological age has also been reported in children whose parents smoke. Among the main components of tobacco smoke are nonhalogenated polycyclic aromatic hydrocarbons (PAHs), many of which are highly toxic. Humans are exposed to PAH compounds mainly via tobacco smoke and diet. The aim of our study was to investigate the effect of PAHs on tooth formation and the function of tooth-forming cells. We exposed mouse (NMRI) E18 mandibular first and second molar explants to 7,12-dimethylbenz[a]anthracene (DMBA), a toxic PAH compound, in organ culture for 7 or 12 days. DMBA concentrations used were 0.1, 0.5, 1, and 2 microM. The mesiodistal width of each first molar (12-day culture) was measured in stereomicroscopic images, and the teeth were analysed histologically. DMBA exposure significantly reduced the mesiodistal width of the first molars. DMBA impaired or delayed amelogenesis and dentinogenesis in both molars at the lowest concentration of 0.1 microM. DMBA affected enamel formation more severely than dentin formation and occasionally prevented amelogenesis completely. Elongation and polarization of ameloblasts were impaired, and blood vessel architecture of the dental papilla (future pulp) was altered. Cusps were thin and sharp. In line with the finding that maternal smoking during pregnancy has an adverse effect on child's tooth development, this study shows the toxic influence of PAHs on tooth development in vitro.

9,10-Dimethyl-1,2-benzanthracene↗