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At least 19 recordsLinked to original sources
PubMed1983

Coal tar phototherapy for psoriasis reevaluated: erythemogenic versus suberythemogenic ultraviolet with a tar extract in oil and crude coal tar.

Recent studies have questioned the therapeutic value of coal tar versus ultraviolet (UV) radiation and their relative necessity in phototherapy for psoriasis. In this investigation, different aspects of tar phototherapy have been studied in single-blind bilateral paired comparison studies. The effects of 1% crude coal tar were compared with those of petrolatum in conjunction with erythemogenic and suberythemogenic doses of ultraviolet light (UVB) using a FS72 sunlamp tubed cabinet. Crude coal tar was clinically superior to petrolatum with suberythemogenic ultraviolet. With the erythemogenic UVB, petrolatum was equal in efficacy to crude coal tar. Suberythemogenic UVB was also used adjunctively to compare the effects of a 5% concentration of a tar extract in an oil base to 5% crude coal tar in petrolatum or the oil base without tar. The tar extract in oil plus suberythemogenic UVB produced significantly more rapid improvement than the oil base plus UVB. The direct bilateral comparison of equal concentrations of tar extract in oil base versus crude coal tar in petrolatum in a suberythemogenic UV photo regimen revealed no statistical differences between treatments. In a study comparing tar extract in oil and the oil base without ultraviolet radiation, the tar extract in oil side responded more rapidly. This demonstrates a direct effect of tar alone in therapy. We have also studied the effects of erythemogenic and suberythemogenic UVB with and without tar extract in oil in the hairless mouse epidermal deoxyribonucleic acid (DNA) synthesis suppression assay. It was found that erythemogenic dosages of UVB produced near maximal inhibition of DNA synthesis with or without coal tars. Suberythemogenic dosages of UVB produced submaximal suppression of DNA synthesis that was enhanced by adjunctive coal tar but not by vehicle, findings which are consistent with the above clinical results. These studies suggest that coal tars combined with suberythemogenic UVB therapy is a practical alternative (to more aggressive UVB therapy without coal tar) which reduces the UVB exposure to the patient.

Animals↗
PubMed2003

Molecular dynamics reveals the stabilizing role of loop closing residues in kissing interactions: comparison between TAR-TAR* and TAR-aptamer.

A RNA aptamer (R06) raised against the trans- activation responsive (TAR) element of HIV-1 was previously shown to generate a loop-loop complex whose stability is strongly dependent on the selected G and A residues closing the aptamer loop. The rationally designed TAR* RNA hairpin with a loop sequence fully complementary to the TAR element, closed by U,A residues, also engages in a loop-loop association with TAR, but with a lower stability compared with the TAR-R06 complex. UV absorption monitored thermal denaturation showed that TAR-TAR*(GA), in which the U,A kissing residues were exchanged for G,A, is as stable as the selected TAR-R06 complex. Consequently, we used the TAR-TAR* structure deduced from NMR studies to model the TAR-R06 complex with either GA, CA or UA loop closing residues. The results of the molecular dynamics trajectories correlate well with the thermal denaturation experiments and show that the increased stability of the GA variant results from an optimized stacking of the bases at the stem-loop junction and from stable interbackbone hydrogen bonds.

Base Pairing↗
PubMed2004

Double-blind, randomised, multicentre, parallel group study comparing a 1% coal tar preparation (Exorex) with a 5% coal tar preparation (Alphosyl) in chronic plaque psoriasis.

BACKGROUND: Exorex lotion is a novel formulation of prepared coal tar indicated for the treatment of psoriasis. OBJECTIVES: To compare the efficacy and tolerability of 1% prepared coal tar lotion versus 5% coal tar extract in patients with mild to moderate plaque psoriasis. PATIENTS AND METHODS: This was a double-blind, randomised controlled study. Patients initially entered a 7-day washout period, during which they applied a yellow soft paraffin plus emulsifying wax ointment used as an emollient three times a day to their plaques. They were then randomised to receive treatment with 1% coal tar (Exorex) lotion or 5% conventional coal tar lotion (Alphosyl), three times a day for 12 weeks. Both treatment groups continued to apply the emollient throughout the duration of the study. Two target plaques were selected at entry for assessment. The clinical measures used were: 1) Total Sign Score (TSS), the sum of 5-point rating scores for erythema, induration and scaling averaged for the two target plaques (range 0-12), 2) the Psoriasis Area and Severity Index (PASI), and 3) patient and investigator 7-point global assessments of improvement at 12 weeks. Patients were assessed at 0, 4, 8 and 12 weeks during the treatment period or at the point of withdrawal. Spontaneously reported and observed adverse events were noted. RESULTS: Three hundred and twenty four of 338 randomised patients were evaluable (ITT analysis): 158 patients received 1% coal tar lotion and 166 patients received conventional coal tar. Both groups showed decreases from baseline to end of treatment in mean TSS (decrease of 2.4 points from 5.6 to 3.2 with 1% coal tar lotion and 1.8 points from 5.5 to 3.7 with conventional coal tar), and mean PASI (decrease of 2.4 points with 1% coal tar lotion and 1.5 points with conventional coal tar). Two hundred and twenty eight patients completed the full course of treatment. There was a statistically significant treatment difference in the percentage change in mean TSS at week 12, in favour of 1% coal tar lotion (-10.6%, 95% CI -20.6% to -0.5%, p=0.04). There was also a difference between treatments in the change in mean PASI in favour of 1% coal tar that was of borderline statistical significance (-11.7%, 95% CI -23.8% to 0.4%, p=0.06). Investigator global assessments also favoured 1% coal tar lotion (38% vs. 27% of patients showed clearance or marked improvement). The 1% coal tar lotion had a similar safety profile to 5% conventional coal tar lotion with the majority of treatment-related events being mild to moderate in severity. CONCLUSIONS: 1% coal tar lotion is more effective than a conventional coal tar lotion in mild to moderate psoriasis and may be preferred for first-line topical treatment.

Adolescent↗
PubMed1984

Switching to low tar cigarettes: are the tar league tables relevant?

Representative samples of smokers of regular middle tar and regular low tar cigarettes responded to a questionnaire concerning their smoking habits and participated in a blind product test, returning 24 hour butt collections from the smoking of both middle tar and low tar cigarettes. An estimate of the mouth intake of tar derived from a measurement of filter nicotine confirmed partial compensation by the low tar smokers relative to the middle tar smokers, resulting in 32% lower tar delivery rather than the 46% expected from the standard machine values. Most middle tar smokers (98%) achieved an estimated tar delivery within or below that of the league table middle tar band when smoking middle tar cigarettes, while 70% of low tar smokers had a mouth intake of 10 X 49 mg or below within the low tar band when smoking low tar cigarettes. These results support the current tar league tables as a guide to the smoker in selecting a lower delivery cigarette.

Adolescent↗
PubMed1990

Wood tars allergy, cross-sensitization and coal tar.

In a population of 1883 patients tested for allergic contact dermatitis (1985-1988), a prevalence of 5.4% (103 cases) was seen for wood tars (ICDRG allergen, 12% pet.) sensitization. In this group (n = 103), retrospectively, a combined allergy was seen to wood tars and fragrance mix in 43% and to wood tars and balsam of Peru in 31%. A combined allergy to wood tars and coal tar was seen in 19 patients (18.5%): 14 to liquor carbonis detergens (LCD), 8 to lianthral and 3 to both LCD and lianthral. Within the group with wood tars allergy (n = 103), a minority (n = 37) had a history of atopic dermatitis. Comparison of the test results in atopic and non-atopic subgroups (within the group of 103) revealed a higher incidence of combined wood tars-fragrance mix allergy in the atopic group (n = 37). In this group, a lower incidence of combined wood tars-coal tar sensitization was seen in comparison with the non-atopic group (n = 66). The authors believe that combined "wood tars-coal tar" allergy could be the consequence of cross-sensitization rather than due to long-term previous topical treatment with tar derivatives. The high % of cross-allergy between wood tars and fragrance mix emphasizes the role of wood tars as an important indicator allergen in perfume allergy.

Coal Tar↗
PubMed1992

Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. II. Results of a randomised controlled trial.

STUDY OBJECTIVE: The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN: This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING: 21 local authority districts of England. SUBJECTS: Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS: Changes in the measures of respiratory health showed little difference over the trial period between the three cigarette groups. Analyses of the urinary nicotine metabolites showed that smokers allocated to each of the three study cigarettes adjusted their smoking so that throughout the trial their nicotine inhalation differed little from their pretrial intakes when they were smoking their own cigarettes. As a result of the altered patterns of smoking to compensate for the reduced nicotine yields of the three study cigarettes, the tar intake of those allocated to smoke the middle tar, middle nicotine cigarettes remained essentially unchanged, while those allocated to smoke the low tar, low nicotine and low tar, middle nicotine cigarettes had calculated reductions in tar intakes of about 14% and 18%, respectively. CONCLUSIONS: Due to the phenomenon of compensation, tar intake can only be reduced substantially by using a cigarette with a markedly lower tar/nicotine ratio. Nevertheless reductions of up to about 18% in tar intake failed to result in any detectable effect on respiratory symptoms or peak expiratory flow rates over a six month period.

Adolescent↗
PubMed1997

Distinct transcriptional pathways of TAR-dependent and TAR-independent human immunodeficiency virus type-1 transactivation by Tat.

Tat stimulates HIV-1 gene expression during transcription initiation and elongation. Tat functions primarily through specific interactions with TAR RNA and several putative cellular cofactors to increase the processivity of RNA polymerase II complexes during HIV-1 transcription elongation. Although HIV-1 transactivation by Tat in most cell types requires intact TAR sequences, previous reports demonstrate that Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression in several central nervous system-derived astrocytic/glial cell lines in the absence of TAR. Within this study, transient expression assays performed in the astrocytic/glial cell line, U87-MG, confirm that kappa B elements within the HIV-1 LTR mediate TAR-independent transactivation by Tat and demonstrate additionally that distinct amino acid residues within the cysteine-rich activation domain of Tat are required for TAR-independent versus TAR-dependent transactivation. Established U87-MG cell lines expressing a transdominant negative mutant of I kappa B alpha, I kappa B alpha delta N, fail to support TAR-independent transactivation by Tat, suggesting that binding of NF-kappa B to kappa B enhancer elements within the HIV-1 LTR is necessary for Tat-mediated transactivation in the absence of TAR. Ribonucleic acid protection analyses of promoter-proximal and -distal transcripts derived from TAR-deleted and TAR-containing HIV-1 LTR reporter constructs in U87-MG cells indicate that the predominant effect of Tat during TAR-independent transactivation occurs at the lavel of transcription initiation, whereas a prominent elongation effect of Tat is observed in the presence of TAR. These data suggest an alternative regulatory pathway for Tat transactivation in specific cells derived from the central nervous system that is independent of TAR and that requires direct or indirect interaction of Tat with NF-kappa B-binding sites in the HIV-1 LTR.

Amino Acid Sequence↗
PubMed1992

Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. I. Design of a randomised controlled trial.

STUDY OBJECTIVE: The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN: This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING: 21 local authority districts of England. SUBJECTS: Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS: Postal questionnaires were sent to 265,016 individuals selected from the electoral registers of 21 local authority districts of England; 64% of questionnaires were returned revealing 7736 men aged 18-44 years who smoked only middle tar cigarettes. Of these, 7029 (90%) were sent a health warning and 707 (10%) were not; the latter acted as a control group to assess the effect of the health warning. Of the 7029 men who had received a health warning and were visited at the recruitment stage, 2666 agreed and were eligible to participate in the trial although only 1541 (58% of those who agreed and were eligible) actually started smoking the study cigarettes; 643 men (24% of those willing to participate at the beginning of the trial and 42% of those who actually started smoking the study cigarettes) completed the trial smoking the study cigarettes. Of these, 213 were in the low tar middle nicotine group, 220 were in the middle tar middle nicotine group, and 210 were in the low tar low nicotine group. CONCLUSIONS: This study shows the feasibility of identifying and recruiting sufficient numbers of male middle tar smokers, with adequate numbers completing the trial, to detect any changes in respiratory health over a six month period.

Adolescent↗
PubMed2002

Specific HIV-1 TAR RNA loop sequence and functional groups are required for human cyclin T1-Tat-TAR ternary complex formation.

Replication of human immunodeficiency virus requires Tat protein which activates elongation of RNA polymerase II transcription at the HIV-1 promoter through interaction with the cyclin T1 (CycT1) subunit of the positive transcription elongation factor complex (P-TEFb). Tat binds directly through its transactivation domain to the CycT1 subunit of the P-TEFb and induces loop sequence specific binding of the P-TEFb onto nascent HIV-1 TAR RNA. By using a gel electrophoresis method and a comprehensive set of TAR loop mutants, we have identified the sequence and structural determinants for high-affinity CycT1-Tat-TAR ternary complex formation. Our results show that CycT1 and Tat binding to TAR RNA is highly cooperative, and a capacity of 85%, a Hill coefficient of 2.7, and a dissociation constant (K(D)) of 2.45 nM were observed. These results indicate that there are three binding sites on TAR RNA. CycT1 does not bind TAR RNA in the absence of Tat, and Tat binding to TAR, while detectable, is very inefficient in the absence of CycT1. It is conceivable that the CycT1-Tat heterodimer directly binds to TAR RNA in the U-rich RNA bulge region and this binding facilitates the interactions of the CycT1-Tat heterodimer at the other two sites in the RNA loop region. On the basis of our results, we suggest a model where CycT1 interacts with Tat protein and positions the protein complex to make contacts with the G34 region of the loop sequence; G34 is critical for CycT1-Tat binding and forms a C30.G34 base pair. Two functional groups, O6 and N7, at nucleotide positions 32 and 34 in the TAR loop are essential for CycT1-Tat interactions with TAR RNA. The identity of two nucleotides, U31 and G33, is not critical, but they contribute to the stabilization of the RNA-protein complex. The presence of a single-nucleotide bulge of A35 or C35 is essential for distortion of the backbone RNA structure as well as the accessibility of functional groups in the major groove of the double-helical region. CycT1-Tat interaction with TAR RNA represents another example of the flexibility and complexity of RNA structure involved in protein recognition.

Base Sequence↗
PubMed2002

The TAR RNA-binding protein, TRBP, stimulates the expression of TAR-containing RNAs in vitro and in vivo independently of its ability to inhibit the dsRNA-dependent kinase PKR.

TRBP (HIV-1 transactivating response (TAR) RNA-binding protein) and PKR, the interferon-induced dsRNA-regulated protein kinase, contain two dsRNA binding domains. They both bind to HIV-1 TAR RNAs through different sites. Binding to dsRNA activates PKR that phosphorylates the eukaryotic initiation factor eIF-2alpha leading to protein synthesis inhibition. TRBP and PKR can heterodimerize, which inhibits the kinase function of PKR and has a positive effect on HIV-1 expression. In this study, an in vitro reticulocyte assay revealed the poor expression of TAR containing CAT RNAs compared with CAT RNAs. Addition of TRBP restored translation efficiency of TAR-CAT RNA and decreased the phosphorylation status of eIF-2alpha, confirming its role as a PKR inhibitor. Unexpectedly, eIF-2alpha was phosphorylated in the presence of TAR-CAT as well as CAT RNA devoid of the TAR structure. TRBP inhibited eIF-2alpha phosphorylation in both cases, suggesting that it restores the translation of TAR-CAT RNA independently and in addition to its ability to inhibit PKR. TRBP activity on gene expression was then analyzed in a PKR-free environment using PKR-deficient murine embryo fibroblasts. In a transient reporter gene assay, TRBP stimulated the expression of a TAR-containing luciferase 3.8-fold whereas the reporter gene with mutated TAR structures or devoid of TAR was stimulated 1.5- to 2.4-fold. Overall, the activity of TRBP2 was higher when the 5'-end of the mRNA was structured and was mediated independently by each dsRBD in TRBP. Increasing concentrations of TRBP showed no significant modification of the luciferase RNA levels, suggesting that TRBP stimulates translation of TAR-containing RNAs. Therefore, TRBP is an important cellular factor for efficient translation of dsRNA containing transcripts, both by inhibiting PKR and in a PKR-independent pathway.

Animals↗
PubMed1995

The tar reduction study: randomised trial of the effect of cigarette tar yield reduction on compensatory smoking.

BACKGROUND: Observational and short term intervention studies have reported that smokers of low tar cigarettes inhale more deeply (that is, compensate) than those who smoke high tar cigarettes. To quantify this effect a long term randomised trial was conducted on the effects of switching to low tar cigarettes. METHODS: The trial was carried out between April 1985 and March 1988 among cigarette smokers in the British Civil Service, measuring blood carboxyhaemoglobin (COHb) levels and serum cotinine levels as markers of tobacco smoke intake. Volunteers first switched to a cigarette brand yielding around 10% less tar than their usual brand to identify smokers able to change brand. The 434 subjects who successfully switched were then randomly allocated to one of three groups: (a) "fast reduction" group which changed to a brand of cigarettes with a tar yield of about half that of their usual brand; (b) "slow reduction" group which reduced to the same level in steps over several months; and (c) a control group which continued smoking cigarettes with a tar yield 10% lower than their usual brand. RESULTS: Over the course of the trial cigarette consumption declined slightly in all three groups. In both the "fast reduction" and the "slow reduction" groups, intake of COHb and cotinine was reduced, though not to the same extent as the yield reduction. Comparison of the results before randomisation with those at the end of the trial showed that a reduction in carbon monoxide yield of 45% was associated with a decrease in carbon monoxide intake of 19% (95% confidence interval 14% to 24%) and that a reduction in nicotine yield of 40% was associated with an 11% (6% to 16%) reduction in nicotine intake, reflecting relative intakes of about 1.5 for both carbon monoxide and nicotine in the "fast reduction" group. Results were similar in the "slow reduction" group with a 42% reduction in carbon monoxide yield, a 16% (11% to 22%) reduction in carbon monoxide intake, a 37% reduction in nicotine yield, and a 6% (0% to 13%) reduction in nicotine intake. Estimates of compensation derived from these results were 65% for carbon monoxide, 79% for nicotine, and 62% for tar. CONCLUSIONS: Compensation, demonstrated when switching from a high tar cigarette to a low tar one, was incomplete. Advising people who have failed to give up smoking to switch to low tar cigarettes will reduce the intake of smoke constituents to a small extent. This would be expected to decrease their risk of smoking-related diseases, although by a smaller amount than would be achieved by giving up smoking altogether.

Adaptation, Psychological↗
PubMed2001

The specific hydrolysis of HIV-1 TAR RNA element with the anti-TAR hammerhead ribozyme: structural and functional implications.

The main transcriptional regulator of the human immunodeficiency virus is the Tat protein, which recognises and binds to a fragment RNA at the 5' end of viral mRNA, named transactivation response element (TAR) RNA. Extensive mutagenesis studies have shown that a region of TAR RNA important for Tat binding involves a set of nucleotides surrounding a characteristic UCU nucleotide bulge. The specific Tat-TAR complex formation enhances the rate of transcription elongation but inhibition of that interaction prevents the human immunodeficiency virus type 1 (HIV-1) replication. If so, a possibility of virus inactivation would be a site specific degradation of the TAR RNA element. To break down and inactivate TAR RNA, we designated the anti-hammerhead (HH) ribozyme to cleave nucleosides within the bulge. We showed for the first time the new type of the AUC hammerhead ribozyme, which hydrolyses specifically the TAR RNA element at C8 nucleotide in the bulge (C24 in the standard TAR RNA numbering). The cleavage reaction has broad magnesium requirements. Mn and particularly Ca are less efficient. Argininamide interferes with the cleavage of TAR RNA induced by the ribozyme. These results have two implications; (i) structural, where the HIV-1 TAR RNA element in solution occurs in equilibrium of only two forms, one of which, a double stranded RNA, meets structural requirements for ribozyme pairing and cleavage, and (ii) functional, the HH ribozyme can be explored for an inactivation of HIV-1 through the TAR RNA element deintegration.

Arginine↗
PubMed1986

Reduction of tar, nicotine and carbon monoxide intake in low tar smokers.

Blood nicotine, cotinine, and carboxyhaemoglobin (COHb) concentrations were measured in 392 smokers (255 women and 137 men) of "middle tar" (17-22 mg), "low to middle" (11-16 mg), and "low tar" (less than 11 mg) cigarettes. Since tar intake cannot yet be measured directly, we devised an index to estimate it based on the use of measured levels of an intake marker (eg, blood nicotine) and the ratio of the tar to marker yields of the cigarettes. This approach was validated by its ability to enhance the prediction of levels of one marker by use of another. In a practical test, using COHb and the CO/nicotine yield ratio of the cigarettes, the mean blood nicotine concentration of the low tar smokers was predicted to be 31.9 ng/ml compared with the measured mean of 31.8 ng/ml. Our main findings were that despite substantial compensatory increases in inhalation, the low tar smokers took in about 25% less tar, about 15% less nicotine, and about 10% less carbon monoxide than smokers of middle and low to middle tar cigarettes. These results indicate that low tar cigarettes of the type available in Britain since the late 1970s are likely to prove less harmful than other brands. Monitoring of smoke intakes could supplement epidemiological approaches and provide earlier evidence of whether changing cigarette designs lead to any significant dosage reduction that could affect the risk of disease.

Carbon Monoxide↗
PubMed1996

Coal tar, pine tar and sulfonated shale oil preparations: comparative activity, efficacy and safety.

BACKGROUND: Tar and sulfonated shale oil preparations are used in the treatment of a variety of inflammatory skin diseases, including psoriasis vulgaris; due to the high polycyclic aromatic hydrocarbon (PAH) content of tars, a possible relationship with cancer in humans has been postulated. On the other hand, the purity of sulfonated shale oils concerning PAHs guarantees a good tolerability during dermatologic therapy. AIM: In this review, it is attempted to compare activity, efficacy and safety of coal tar, pine tar and sulfonated shale oil preparations which currently play a role in dermatologic treatment. RESULTS AND CONCLUSIONS: Primary sources of PAHs in the normal human environment are forest fires, cigarette smoke and combustion of fossil fuels for heating and energy. Thermal processing of fossil substances is also required for the production of tars and sulfonated shale oils. Due to individual manufacturing techniques, tars and sulfonated shale oils differ completely in their chemical composition. Still, sulfonated shale oils are often falsely grouped as tars because of their related origin and similar dermatologic indications. There is at least limited evidence of the activity and efficacy of various tars as well as sulfonated shale oil preparations in different frequent inflammatory skin diseases. This includes psoriasis vulgaris and atopic eczema of glabrous as well as hairy skin. There is still some concern about the long-term tolerability of tar preparations at least in some contexts. This, however, does not apply to sulfonated shale oil preparations. Consequently, at least their use should still be considered a rational drug treatment in dermatology.

Animals↗
PubMed2001

Comparative analysis of PAH:DNA adducts formed in lung of mice exposed to neat coal tar and soils contaminated with coal tar.

7H-Benzo[c]fluorene (benzo[c]fluorene) is a major DNA adduct forming component of coal tar in lung of mice. The present study evaluated the types of PAH:DNA adducts formed from different neat coal tar samples and soils contaminated with coal tar. Mice were fed diets containing coal tar either neat or as a contaminant in an environmental soil sample for 14 days, and the types of chemical:DNA adducts formed in lung were evaluated using 32P-postlabeling and HPLC analysis. Three major DNA adducts derived respectively from benzo[b]fluoranthene (B[b]F), benzo[a]pyrene (B[a]P), and benzo[c]fluorene were detected in three of the four neat coal tar samples evaluated. In contrast, only a single major DNA adduct derived from benzo[c]fluorene was observed with the remaining tar sample. Ingestion of coal tar contaminated soil resulted in DNA adducts primarily derived from benzo[c]fluorene and B[b]F; a B[a]P derived DNA adduct was not detected. The DNA adducts derived from benzo[c]fluorene and B[b]F but not B[a]P were also observed with animals fed methylene chloride extracts of three of these soils but not the one designated A1000H soil. However, the extract of A1000H resulted in a B[a]P:DNA adduct being detected along with adducts formed from B[b]F and benzo[c]fluorene. The selective formation of the benzo[c]fluorene:DNA adduct with coal tar contaminated soils indicates that the in vivo systemic bioavailability and/or metabolism of benzo[c]fluorene is relatively high when compared to other DNA adducting hydrocarbons within coal tar. Benzo[c]fluorene may play a critical role in the potential of contaminated soil to induce a toxicological response in animals.

Administration, Oral↗
PubMed1990

Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar.

Preparations of coal-tar and juniper tar (cade oil) that are used in the treatment of psoriasis are known to contain numerous potentially carcinogenic polycyclic aromatic hydrocarbons (PAH). Evidence of covalent binding to DNA by components of these mixtures was sought in a) human skin biopsy samples from 12 psoriasis patients receiving therapy with these agents, b) human skin explants maintained in organ culture and treated topically with the tars, and c) the skin and lungs of mice treated with repeated doses of the formulations following the regimen used in the clinic. DNA was isolated from the human and mouse tissues and digested enzymically to mononucleotides. 32P-Post-labeling analysis revealed the presence of aromatic DNA adducts in the biopsy samples at levels of up to 0.4 fmol total adducts/microgram DNA. Treatment of human skin in organ culture produced similar levels of adducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls. In mouse skin, coal-tar ointment and juniper tar gave similar DNA adduct levels, with a similar time-course of removal: maximum levels (0.5 fmol/microgram DNA) at 24 h after the final treatment declined rapidly to 0.05 fmol/microgram at 7 d, thereafter declining slowly over the succeeding 25 d. However, while coal-tar ointment produced only very low levels of adducts in mouse lung (less than 0.03 fmol/microgram DNA), juniper tar produced adducts at a high level (0.7 fmol/microgram DNA) that were persistent in this tissue. These results provide direct evidence for the formation of potentially carcinogenic DNA damage in human and mouse tissue by components of these therapeutic tar preparations.

Administration, Topical↗