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H Bartsch

Publications and source records attributed to H Bartsch.

At least 19 recordsLinked to original sources
PubMed1992

An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity.

An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(a)pyrene (BP) tetrols released after acid hydrolysis of lung DNA from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatography was determined by chromatography in two different solvent systems and fluorescence spectroscopy. This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy- 7,8,9,10-tetrahydro-BP, requires 100-500 micrograms of DNA, and can measure 1 adduct/10(8) unmodified nucleotides. As this assay does not use immunoaffinity chromatography or solvent extraction, it allows a > 90% recovery of benzo(a)pyrene diol-epoxide-DNA adducts. This procedure has been tested on 13 DNA samples prepared from nontumorous lung parenchyma taken from lung cancer patients at surgery and revealed the presence of DNA adducts of the anti-benzo(a)pyrene diol-epoxide in 9 of 11 samples from smokers and in 2 of 2 ex-smokers. In only two samples from smokers the formation of adducts derived from syn-benzo(a)pyrene diol-epoxide was detected. A 15-fold variation in DNA adduct level was found in 11 of 13 DNA samples, with a range of 0.6-9.9 adducts of benzo(a)pyrene diol-epoxide/10(8) nucleotides. In samples containing both anti- and syn-benzo(a)pyrene diolepoxide-DNA adducts, the anti/syn adduct ratio is 2:1. A highly significant correlation was found between pulmonary microsomal aryl hydrocarbon hydroxylase activity and the level of benzo(a)pyrene diolepoxide-DNA adduct (r = 0.91; P < 0.001; n = 13). A crude linear correlation between the amounts of these adducts and those of bulky DNA adducts determined by 32P-postlabeling assay was observed in the same samples (r = 0.78; P < 0.02; n = 13). Thus this highly sensitive and specific procedure is suitable for measuring benzo(a)pyrene diolepoxide-DNA adducts in human tissues from environmentally exposed subjects and could be adapted to measure polycyclic aromatic hydrocarbons other than BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of primary prostate cancer patients: evidence for reduced pineal activity and relevance of urinary determinations.

The circadian rhythms of melatonin and 6-sulfatoxymelatonin (aMT6s) were analyzed in serum and urine of young men (YM, n = 8), of elderly patients with benign prostatic hyperplasia (BPH, n = 7) and of patients of similar age with primary prostate cancer (PC, n = 9). The data expressed as concentration and in urine also as hourly excreted quantity were analyzed chronobiologically by the single cosinor method and, subsequently submitted to linear regression analyses. Circadian rhythms were detected in all cases except for the excreted quantity of melatonin. The circadian patterns of melatonin and aMT6s in serum were very similar in the different groups and regression analyses showed close correlations between both variables. MESOR and amplitude were significantly depressed in PC (40-60%) as compared to BPH and YM indicating that the depression of serum melatonin in PC is due to a reduced pineal activity and is not caused by an enhanced metabolic degradation in the liver. Acrophases of serum melatonin occurred between 01:34 and 03:26 h and of serum aMT6s between 03:58 and 04:35 h. Circadian rhythms similar to those of serum melatonin and aMT6s were found in urine, particularly for aMT6s excretion as well as melatonin concentration; the determination of both parameters in overnight urine samples closely correlated with the nocturnal peak of circulating melatonin. These results imply that it is feasible to estimate changes in pineal function of prostate cancer patients by means of non-invasive determination using urinary melatonin and aMT6s.

Adult↗
PubMed1992

Levels of direct-acting mutagens, total N-nitroso compounds in nitrosated fermented fish products, consumed in a high-risk area for gastric cancer in southern China.

A high gastric cancer mortality in Fujian province (Peoples Republic of China) has been associated with the consumption of certain salted fermented fish products such as fish sauce (FS). We have investigated the levels and nature of N-nitroso compounds (NOC) and genotoxins present, before and after nitrosation, in 49 FS samples collected from villages in this high-risk area, pooled into six samples. The concentrations of total NOC before nitrosation ranged from 0.2 to 16 mumoles/l, and after nitrosation at pH 2 and pH 7, they rose by up to 4800- and 100-fold, respectively. In nitrosated samples, 40-50% of total NOC was not extractable into organic solvents; volatile N nitrosamines accounted for 1-2% and N-nitrosamino acids for 8-16% of total NOC. None of the FS samples exhibited genotoxic activity, but after nitrosation all were weakly active in the SOS chromotest. The highest SOS-inducing potency was observed with nitrosated ethyl acetate extracts of most samples. The formation of methylating agents was measured by incubation of nitrosated FS with DNA and subsequent analysis of 7-methylguanine adduct. 2 of the 6 nitrosated FS samples caused a slight increase in DNA methylation. 1 pooled home-made FS sample (the only one tested) contained tumour promoter-like substances, as measured by expression of certain EBV genes in Raji cells. HPLC fractionation of ethyl acetate extracts of FS samples allowed identification of three UV-absorbing peaks that, upon nitrosation, produced direct-acting genotoxins. This genotoxicity was partly ascribed to the formation of nitrite-derived arene diazonium cations that were characterized by a coupling reaction with N-ethyl-1-naphthylamine and thin-layer chromatography.

China↗
PubMed1992

Effects of hickory-smoke condensate on development of pepsinogen 1-altered pyloric glands in rats.

Hickory-smoke condensate (HSC) is a popular food flavouring in the USA. Available data have suggested that this food additive has tumour-initiating/promoting potential. Accordingly, a commercial HSC has been investigated for its capacity to promote tumours in the rat glandular stomach using pepsinogen 1 (Pg 1)-altered pyloric glands (PAPG) as the marker of preneoplastic lesions. The development of PAPG initiated by a single intragastric administration of N-methyl-N'-nitroso-N-nitrosoguanidine was significantly increased by feeding rats a diet containing 5% HSC; no effect was observed with lower doses (1.25 or 2.5%) of HSC. The results suggest that HSC has weak tumour-promoting potential in the rat glandular stomach.

Animals↗
PubMed1992

Expression of pulmonary cytochrome P4501A1 and carcinogen DNA adduct formation in high risk subjects for tobacco-related lung cancer.

Cigarette smoking is the strongest risk factor for lung cancer (LC), but genetically determined variations in pulmonary metabolism of tobacco-derived carcinogens may affect individual risk. Results from a case-control study on LC patients demonstrated the pronounced effect of tobacco smoke on pulmonary xenobiotic metabolism and prooxidant state, and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated LC: LC patients who were recent smokers had significantly induced BP-3-hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECDE) activities in lung parenchyma, when compared with smoking non-cancer patients. In recent smokers, lung AHH activity was positively correlated with the level of tobacco smoke-derived DNA adducts as determined by 32P-postlabelling. Pulmonary AHH activity also showed a good correlation with the intensity of immunohistochemical staining for cyt. P4501A by a monoclonal Ab in lung tissue sections: smoking and peripheral type of lung cancers were positively related to high levels of this cyt. P450 species, probably reflecting high rates of induction. These results suggest that high pulmonary CYP1A1 expression (controlling in part carcinogen DNA-adduct formation) in tobacco smokers, appears to be associated with LC risk. High risk subjects may thus be identifiable through genotyping assays for CYP1A1 polymorphism.

Aryl Hydrocarbon Hydroxylases↗
PubMed1992

Substances in human urine that strongly inhibit bacterial mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and related heterocyclic amines.

Extracts of human urine were shown to contain substances that strongly inhibited the liver S9-mediated mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Salmonella typhimurium TA98 strain in a liquid incubation assay. The inhibitory effect was unrelated to cytotoxicity and was similar with urine extracts from smokers and non-smokers. Under similar assay conditions, the mutagenicity of the related amino-imidazoazaarenes, 2-amino-3-methyl-imidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was also found to be strongly inhibited by urine extracts. Decreased or enhanced mutagenicity was seen with 2-acetyl-aminofluorene and 2-aminoanthracene depending on the type of assay, and the time of incubation in liquid medium. A weak inhibition of the mutagenicity of 2-nitrofluorene, a direct-acting mutagen, was observed only after a short incubation time. Mutagenicity of 4-nitroquinoline N-oxide was not altered by the presence of urine extracts at concentrations shown to be inhibitory for the mutagenicity of heterocyclic aromatic amines. Our data suggest that the inhibitory substances in urine act through their capacity to non covalently bind the parent heterocyclic and aromatic amines, thus affecting their availability in aqueous medium for diffusion into liver microsomes where metabolic activation takes place.

Amines↗
PubMed1992

Etheno adducts formed in DNA of vinyl chloride-exposed rats are highly persistent in liver.

Preweanling rats were exposed to 600 p.p.m. (4h/day) of the human carcinogen vinyl chloride for 5 days to determine the molecular dosimetry of DNA adducts in liver, lung and kidney. 7-(2'-Oxoethyl)guanine (7OEG) was the major DNA adduct detected, representing approximately 98% of all adducts. N2,3-Ethenoguanine (epsilon G) and 3,N4-etheno-2'-deoxycytidine (epsilon dC) were present at approximately 1% of the 7OEG concentration, while 1,N6-etheno-2'-deoxyadenosine was present in even lower concentrations. Liver had 3- to 8-fold higher amounts of the DNA adducts than lung and kidney. The persistence of all four adducts was determined at 3, 7 and 14 days post-exposure. Whereas 7OEG had a t 1/2 of -62 h, all three etheno adducts were highly persistent. After accounting for dilution due to growth-related cell proliferation, epsilon G had a t 1/2 of approximately 30 days, while epsilon dC and epsilon dA were not repaired. These data suggest that these cyclic adducts are poorly recognized by liver DNA repair enzymes and have the potential for accumulation upon chronic exposure. This, coupled with the known miscoding properties of the ethenobases, provides a strong rational for examining their role in vinyl chloride-induced cancer and their utility as biomarkers of exposure.

Animals↗
PubMed1992

Carcinogenic tobacco-specific nitrosamines are present at unusually high levels in the saliva of oral snuff users in Sudan.

Exposure to tobacco-specific nitrosamines (TSNA) has been measured in the saliva of 12 users of Sudanese oral snuff (toombak). Using GC coupled to thermal energy analysis, levels of N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were measured before, during and after snuff taking. In addition, two TSNA, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL), were detected in the saliva of tobacco chewers for the first time and were confirmed by GC-MS. Nine out of 10 subjects had detectable saliva levels of total TSNA before chewing (0.01-1.0 micrograms/ml) and immediately following chewing (0.1-2.6 micrograms/ml). During dipping, TSNA concentrations reached microgram/ml levels; (range; number of subjects positive) NNN: (0.6-2.1; 12/12), NAT (0.06-0.5; 2/12), NAB (0.05-1.9; 12/12), NNK (0.06-6.7; 11/12), NNAL (0.05-3.3; 11/12) and iso-NNAL (0.07-0.4; 8/12). These saliva TSNA levels, which are 10-100 times the levels previously reported, are consistent with recent observations of unusually high TSNA levels in Sudanese toombak. As several of these TSNA have been shown to be carcinogenic in animals and epidemiological studies have associated human snuff use with tumours of the oral cavity, these findings draw attention to a significant potential public health hazard.

Adolescent↗
PubMed1992

Stereoselective metabolism of (-)-benzo[a]pyrene-7,8-diol by human lung microsomes and peripheral blood lymphocytes: effect of smoking.

Benzo[a]pyrene (B[a]P)-tetrols formed after stereoselective cytochrome P450-dependent metabolism from (-)-trans-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene [(-)-B[a]P-7, 8-diol] by lung microsomes (n = 19) and peripheral blood lymphocytes (n = 13) from lung cancer patients were measured, and the effect of smoking explored. B[a]P-tetrols were quantified by an HPLC/fluorescence assay with a detection limit of approximately 300 attomol, after incubation with peripheral blood lymphocytes or microsomes from lung cancer patients who were current cigarette smokers, ex-smokers and non-smokers. In lymphocytes from these subjects, high, medium and low metabolic activities respectively for (-)-B[a]P-7,8-diol to tetrol conversion were found, but there was no statistically significant difference between smokers, ex-smokers and non-smokers. When the B[a]P-tetrol formation by human lung microsomes was measured, recent smokers had 4- to 7-fold higher (P = 0.04) metabolic activity than ex-smokers and non-smokers. The mean lung microsomal arylhydrocarbon hydroxylase (AHH) activity was three times higher in smokers than in non-smokers and was undetectable in ex-smokers. AHH activity was correlated with tetrol formation in the same lung microsomal samples (r = 0.62, P less than 0.01 in smokers; and r = 0.67, P less than 0.01 in all subjects). When subjects were grouped according to smoking habits, however, no correlation was detected between mean tetrol formation by lung microsomes and that of lymphocytes. Thus, lymphocytes cannot serve as a surrogate for lung microsomes concerning the pulmonary metabolism of (-)-B[a]P-7,8-diol. The much higher B[a]P-tetrol formation observed in lung microsomes from smokers is in accord with a reported higher pulmonary AHH activity, cytochrome P450IA level, and CYP1A1 gene expression in recent tobacco smokers.

Adolescent↗
PubMed1992

Endogenously formed N-nitroso compounds and nitrosating agents in human cancer etiology.

Humans are exposed to preformed N-nitroso compounds (NOC), but also to a wide range of precursors and nitrosating agents which can react in vivo to form potentially carcinogenic NOC and diazo compounds. Nitrite, nitrate and nitrosating agents can also be synthesized endogenously in enzymic reactions mediated by bacteria, activated macrophages and neutrophils. The latter two cell types generate, via the enzyme nitric oxide synthase, the nitric oxide radical that is involved in cytotoxicity, and is believed to be involved in formation of carcinogenic nitrosamines, DNA base deamination and oxidative damage. Thus endogenous NOC formation, DNA damage and gene mutations in humans could occur at various sites of the body such as the stomach and chronically infected or inflamed organs. Sensitive procedures to estimate the exposure of humans to NOC have been developed and applied in ecological and cross-sectional studies. These have shown that inhabitants of high-risk areas for stomach and esophageal cancer, patients with urinary tract infections (at risk for bladder cancer) and Thai subjects infected with liver fluke (at risk for cholangiocarcinoma) had significantly higher exposure to endogenous NOC. Clinical studies have examined the model of stomach carcinogenesis based on intragastric nitrosation, but the precise roles of bacterial overgrowth and of Helicobacter pylori infection in NOC synthesis and/or inducing oxidative stress in stomach mucosa remain to be clarified. Together these results support the role of NOC and other nitrite-derived mutagens in human cancer etiology, in particular when exposure starts early in life and persists over a long period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct↗
PubMed1992

Drug metabolism in rats with cancer induced by N-nitrosodiethylamine and phenobarbital.

The metabolism of R- and S-warfarin in vivo and in vitro, bufuralol in vitro, and antipyrine and debrisoquine in vivo were studied in rats with cancer induced by N-nitrosodiethylamine and phenobarbital treatment. Microsomal cytochrome P-450 content was greatly reduced in both healthy and cancerous parts of the livers of tumour-bearing animals. The specific activities of R-warfarin and bufuralol 1'-hydroxylases were significantly elevated in rats with cancer. The activities of S-warfarin hydroxylases expressed per mg microsomal protein were reduced in animals with cancer, whereas those of R-warfarin and bufuralol 1'-hydroxylases were not. The urinary excretion of R-7-hydroxywarfarin was increased and those of S-6- and S-4'-hydroxywarfarin decreased in rats with cancer. The correlations between microsomal formation and urinary excretion of all warfarin metabolites were poor, except for R-7-hydroxywarfarin. Antipyrine oxidation was increased in the cancerous state but the urinary metabolic profiles were similar in rats with cancer and in controls. The metabolism of debrisoquine was decreased in tumour-bearing animals. Antipyrine metabolism did not show any correlation with either warfarin or debrisoquine metabolism, whereas several relationships were observed between warfarin and debrisoquine metabolism and between warfarin and bufuralol metabolism.

Animals↗
PubMed1992

Antitumor activity of the pineal gland: effect of unidentified substances versus the effect of melatonin.

There is growing evidence that the pineal gland has antineoplastic properties which, however, can only partially be attributed to its hormone melatonin. While the in vivo tumor-inhibiting activity of melatonin is established, observations on its in vitro effects have been contradictory. The effect of this substance was investigated on six human cancer cell lines and compared to the activity of a partially purified, melatonin-free low molecular weight pineal extract (UMO5R). Melatonin showed hardly any effect but UMO5R was capable of inhibiting the growth of all the six cell lines tested. It is therefore concluded that a direct inhibiting action on tumor cells is not a general physiological role of melatonin as opposed to UMO5R. It will be worthwhile to purify the yet unidentified pineal antitumor activity since it may have a considerable therapeutic potential.

Humans↗
PubMed1992

Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Immunohistochemical detection of pulmonary cytochrome P450IA and metabolic activities associated with P450IA1 and P450IA2 isozymes in lung cancer patients.

The main polycyclic aromatic hydrocarbon-inducible cytochrome P450 was studied in lung tissue from 57 lung cancer patients by immunohistochemistry, using a monoclonal antibody (1-7-1) that recognizes P450IA1 and P450IA2 isozymes. The intensity of immunostaining was compared with the pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), and with P450IA2-related metabolic activity estimated from the ratio of caffeine metabolites in urine. Immunostaining was not observed in peripheral lung tissue of nonsmokers or ex-smokers but was seen in the bronchiolar and alveolar epithelium of all patients who were smokers and had a peripheral carcinoma (16/16) and of 60% (10/17) of those who had a bronchial carcinoma. AHH activity was positively related to the intensity of immunostaining, and an almost 2-fold increase due to smoking was detected in the ratios of caffeine metabolites. These results demonstrate that tobacco smoke induces P450IA1 in the lung and probably P450IA2 in the liver, and suggest a role for certain metabolic phenotypes of P450IA1 in peripheral pulmonary carcinoma.

Adenocarcinoma↗
PubMed1992

Role of lime in the generation of reactive oxygen species from betel-quid ingredients.

The role of lime in the formation of reactive oxygen species (ROS), i.e., O2-., H2O2, and OH., from betel-quid components (extracts of areca nut and catechu) was investigated in vitro using a chemiluminescence technique and an assay for oxidative DNA damage involving analysis of 8-hydroxy-2'-deoxyguanosine. Of the various areca-nut extracts, the catechin fraction, at alkaline pH, was shown to be the most active producer of ROS. The free Ca(OH)2 content and pH of lime samples (a component of betel quid and chewing tobacco) were highly correlated with the generation of ROS from areca-nut extract in vitro and with oxidative base damage to DNA in vitro. While Fe2+ had an enhancing effect on ROS formation, Mg2+ had a marked inhibitory effect. The cytogenetic effects of ROS generated in vivo were measured in Syrian golden hamsters in which the cheek pouch had been painted with lime and an areca-nut extract or catechu, singly or in combination. The frequency of micronucleated cells was increased only in animals that had received both the areca-nut extract and lime. The frequency of micronucleated cells in exfoliated oral mucosal cells from Indian chewers of betel quid with tobacco containing lime or of tobacco with lime was significantly higher than in a control (no habit) group. These studies demonstrate that addition of lime to betel quid constituents generates ROS, which induce cytogenetic damage in hamster cheek pouch and may contribute to the cytogenetic damage observed in the oral cavity of betel-quid chewers. These results implicate ROS in clastogenesis and probably in the etiology of oral cancer.

Animals↗
PubMed1992

Blue rayon.

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Amines↗
PubMed1991

Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand.

Cholangiocarcinoma (CCA) is one of the most common cancers in north-east Thailand and has been associated with infestation by the liver fluke Opisthorchis viverrini (OV). Two samples of 12-hr overnight urine (after dosing with proline and ascorbic acid or proline alone) were collected from 20 inhabitants from each of 5 contrasting incidence areas for CCA. The incidence of CCA was not correlated with either the amount of NPRO or other nitrosamino acids, endogenous nitrosation potential (difference in NPRO levels between proline dose and proline and ascorbic dose), or nitrate level. However, when urinary levels of nitrosamino acids were compared in subjects living in high-risk areas, subjects who were positive for OV antibody excreted significantly more (p less than 0.01) NPRO (12.3 +/- 18.7 micrograms/12 hr) after proline ingestion than those who were negative (3.5 +/- 3.2 micrograms/12 hr). After ingestion of ascorbic acid, the NPRO levels in the positive subjects were significantly reduced (p less than 0.01) to 2.4 +/- 2.0 micrograms/12 hr, suggesting that endogenous nitrosation of proline was inhibited. Thus, endogenous nitrosation potential estimated from the difference between NPRO and the sum of nitrosamino acids excreted in the 2 urine samples was significantly higher in subjects positive for the OV antibody. Small amounts of pre-formed nitrosamines were found in fermented fish and pork food items, which are consumed frequently in the high-risk area for CCA. These results suggest that the interaction between chemical carcinogens, especially nitrosamines, and OV infestation may play a role in the development of cholangiocarcinoma in Thailand.

Adenoma, Bile Duct↗