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S Amin

Publications and source records attributed to S Amin.

At least 181 records · Page 10Linked to original sources
PubMed1988

Synthesis and mutagenicity of 5-alkyl-substituted chrysene-1,2-diol-3,4-epoxides.

In order to explore the relationship between structure and mutagenicity of bay region diol-epoxides of chrysene substituted with an alkyl group in the bay region, we compared the mutagenicity in Salmonella typhimurium TA 100 of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene with its 5-methyl, 5-ethyl and 5-propyl derivatives. The results showed that anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (7400 revertants/nmol) was the most mutagenic of these diol-epoxides followed by anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene and its 5-ethyl derivative (1100 revertants/nmol). The 5-propyl substituted diol-epoxide was inactive at the doses tested. The results demonstrate that steric factors are dominant in the expression of methylchrysene diol-epoxide mutagenicity in S. typhimurium and suggest that the molecular shape of the 5-methyl substituted diol-epoxide leads to a unique reaction with DNA associated with high mutagenicity and tumorigenicity.

Chrysenes↗
PubMed1988

Metabolism and mutagenic activity of benzo[k]fluoranthene and 3-, 8- and 9-fluorobenzo[k]fluoranthene.

The metabolism of 3-, 8- and 9-fluorobenzo[k]fluoranthene (B[k]F) relative to B[k]F was investigated. The major metabolites of B[k]F formed in vitro using rat liver S-9 metabolism systems were 8,9-dihydro-8,9-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 3-, 8- and 9-hydroxyB[k]F. Fluorine substitution within the structure of B[k]F substantially altered the types of metabolites formed in vitro. The most pronounced effect was observed with 9-fluoroB[k]F. In contrast to B[k]F, the 8,9-dihydro-8,9-dihydroxy-, 9-hydroxy- and 10,11-dihydro-10,11-dihydroxy derivatives were not detected as metabolites of 9-fluoroB[k]F. However, either the 2,3- or 4,5-dihydrodiol of 9-fluoroB[k]F was detected. In the case of 8-fluoroB[k]F, neither the 8- nor 11-hydroxy- derivatives were detected. The principle dihydrodiols formed from 8-fluoroB[k]F were the 10,11-dihydrodiol and either the 2,3-or 4,5-dihydrodiol. The pattern of metabolites formed with 3-fluoroB[k]F was similar to that observed with B[k]F with the exception that neither the 3- nor 4-hydroxy derivatives were formed. Mass spectral data indicated that fluoro substitution is not lost to any appreciable extent during the metabolism of 3-, 8- and 9-fluoroB[k]F. The mutagenic activity of these B[k]F fluoro derivatives along with B[k]F, 2,3-dihydro-2,3-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 8,9-dihydro-8,9-dihydroxyB[k]F were evaluated in Salmonella typhimurium TA100 in the presence of rat liver S-9 metabolism systems. 3-FluoroB[k]F was more mutagenic than B[k]F, while both 8- and 9-fluoroB[k]F were less active. While the 2,3-dihydrodiol and 2,3-quinone were weakly active, the 8,9-dihydrodiol had similar mutagenic potency to B[k]F.

Animals↗
PubMed1988

Induction of red blood cell destruction by graft-derived antibodies after minor ABO-mismatched heart and lung transplantation.

Heart-lung transplantation (HLT) unlike other solid-organ transplants involves transplantation of a large amount of lymphoid tissue; hence there is considerable potential for graft-versus-host reaction if there is an antigen mismatch between donor and recipient. Due to the shortage of suitable donors, minor ABO-mismatched HLT (group O organs given to A, B, or AB recipients) are performed. Of 84 consecutive HLT at Harefield Hospital, nine fully ABO-matched and nine ABO-mismatched HLT were studied. Six minor ABO-mismatched HLT patients had evidence of immune destruction of recipient's red cells. Haemolysis started from days 4-12 and lasted for a mean of 13 days; in four cases transfusion support was necessary. ABO antibodies incompatible with the recipient ABO antigens, but compatible with the donor, were found in the serum and red cell eluates of these patients. In two cases, these antibodies were detected for over one year after transplantation. These changes were not seen in the fully ABO-matched controls. Our findings suggest that donor-derived lymphocytes from group O organs continue to produce anti-A and/or anti-B after transplantation, and if the recipient is group A, B, or AB, mount a secondary immune response following antigenic stimulation by the recipient's differing ABO antigens. The specific transfusion management of these patients is discussed.

ABO Blood-Group System↗
PubMed1987

Enhancing effect of a bay region methyl group on tumorigenicity in newborn mice and mouse skin of enantiomeric bay region diol epoxides formed stereoselectively from methylchrysenes in mouse epidermis.

The stereochemistry of diol epoxide formation in mouse epidermis upon topical application of [3H]-1R,2R-dihydroxy-1,2-dihydro-5-methylchrysene ([3H]-5-MeC-1R,2R-diol) and [3H]-6-MeC-1R,2R-diol, and the tumorigenicity in mouse skin and in newborn mice of the R,S,S,R and S,R,R,S enantiomers of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (5-MeC-1,2-diol-3,4-epoxide), 5-MeC-7,8-diol-9,10-epoxide, and 6-MeC-1,2-diol-3,4-epoxide were examined. Analysis of tetraols and their derived tetraacetates present in mouse epidermis, 2 h after application of [3H]-5-MeC-1R,2R-diol or [3H]-6-MeC-1R,2R-diol, demonstrated greater than 90% stereoselectivity in formation of 5-MeC-1R,2S-diol-3S,4R-epoxide and 6-MeC-1R,2S-diol-3S,4R-epoxide. Taken together with previous data, these results demonstrate that there is a high degree of stereoselectivity for formation of R,S,S,R enantiomers of 5-MeC- and 6-MeC-1,2-diol-3,4-epoxides in mouse skin. The results of the tumorigenicity studies in mouse skin and in newborn mice clearly demonstrated that 5-MeC-1R,2S-diol-3S,4R-epoxide was the most tumorigenic of the diol epoxide enantiomers tested; 6-MeC-1R,2S-diol-3S,4R-epoxide was inactive. The results of this study show that the high tumorigenicity of 5-MeC compared to 6-MeC is due to the remarkable tumorigenic activity of 5-MeC-1R,2S-diol-3S,4R-epoxide which, in contrast to 6-MeC-1R,2S-diol-3S,4R-epoxide, has a methyl group in the same bay region as the epoxide ring. We propose that such methyl bay region diol epoxides of other carcinogenic methylated polynuclear aromatic hydrocarbons will also show unique tumorigenic properties.

Animals↗
PubMed1987

High stereoselectivity in mouse skin metabolic activation of methylchrysenes to tumorigenic dihydrodiols.

The stereoselectivity of mouse skin metabolic activation to dihydrodiols of the strong carcinogen 5-methylchrysene (5-MeC) and the weak carcinogen 6-methylchrysene (6-MeC) was investigated. Synthetic 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (5-MeC-1,2-diol), 5-MeC-7,8-diol, and 6-MeC-1,2-diol were resolved into their R,R- and S,S-enantiomers by chiral stationary phase high performance liquid chromatography. The absolute configurations of the enantiomers were assigned by their circular dichroism spectra. Using these enantiomers as standards, the metabolism of 5-MeC and 6-MeC in vitro in rat and mouse liver and in vivo in mouse epidermis was investigated. Only the R,R-enantiomers of each dihydrodiol predominated (greater than 90%). The dihydrodiol enantiomers were tested for tumor initiating activity on mouse skin. In each case, the R,R-dihydrodiol enantiomer was significantly more tumorigenic than the S,S-enantiomer. The most tumorigenic compound was 5-MeC-1R,2R-diol; it was significantly more active than either 5-MeC-7R,8R-diol or 6-MeC-1R,2R-diol. The results of this study demonstrate that there is a high degree of stereoselectivity in the metabolic activation of 5-MeC and 6-MeC to proximate tumorigenic dihydrodiols in mouse skin. The bay region methyl group has no effect on the stereoselectivity of activation to 1,2-dihydrodiol metabolites in the chrysene system.

Animals↗
PubMed1987

Formation and tumorigenicity of benzo[b]fluoranthene metabolites in mouse epidermis.

The metabolism in mouse epidermis of benzo[b]fluoranthene (BbF) was studied. [3H]BbF was applied topically, mice were killed at various intervals, and metabolites were extracted from the epidermis and analyzed by h.p.l.c. The major metabolites were identified by comparisons to standards as 4-, 5-, and 6-hydroxyBbF. Sulfate and glucuronide conjugates of these hydroxyBbF were also detected. Minor metabolites included 12-hydroxyBbF, BbF-1,2-diol, and BbF-11,12-diol. BbF-9,10-diol, the only known tumorigenic oxygenated derivative of BbF, was not detected. The further metabolism of BbF-9,10-diol was studied in vitro, using rat liver 9000 g supernatant. The major metabolites were identified by their spectral characteristics as 5- and 6-hydroxyBbF-9,10-diol. Little if any BbF-9,10,11,12-tetraol was detected. 5- and 6-HydroxyBbF-9,10-diol were not detected as metabolites of [3H]BbF in mouse epidermis. Several known and potential BbF metabolites--BbF-1,2-diol, BbF-11,12-diol, BbF-9,10-diol, BbF-9,10-diol-11,12-epoxide, 5- and 6-hydroxyBbF-9,10-diol, 1-hydroxyBbF, 5-hydroxyBbF, and 6-hydroxyBbF--were tested for tumor initiating activity on mouse skin. Among these, only BbF-9,10-diol showed high tumorigenic activity, but no evidence has been obtained for its formation in vivo from BbF. These studies do not support the hypothesis that BbF is metabolically activated through formation of the bay region diol epoxide, BbF-9,10-diol-11,12-epoxide.

Animals↗
PubMed1987

'Pseudo-lymphoid' leukaemia with unusual features: ultrastructural, immunological, cytogenetic and molecular studies.

An unusual case of 'pseudo-lymphoid' leukaemia is described. The leukaemic cells resembled small, mature lymphocytes but lacked B- and T-cell membrane markers as well as immunoglobulin (Ig) and T-cell receptor gene rearrangements. They showed, instead, features of early myeloid cells since they expressed 2 myeloid antigens, CDW13 and My9, and displayed peroxidase activity demonstrable by electron microscopy (EM) on unfixed cells. Cytogenetic studies showed monosomy 5, t(4;17) (p12;p11), t(2;3)(p23;q14) and an abnormal chromosome 12. Abnormalities of chromosomes 4 and 5 have been previously associated with 'pseudo-lymphoid' leukaemias. This case illustrates the value of sensitive methods for the characterization of blast cells and for the precise diagnosis of leukaemias with apparent 'lymphoid' morphology.

Antibodies, Monoclonal↗
PubMed1986

Synthesis of 6-methylchrysene-1,2-diol-3,4-epoxides and comparison of their mutagenicity to 5-methylchrysene-1,2-diol-3,4-epoxides.

The syn- and anti-isomers of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-methylchrysene (6-MeC-1,2-diol-3,4-epoxide) were synthesized and their mutagenic activities in Salmonella typhimurium were compared with those of the syn- and anti-isomers of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (5-MeC-1,2-diol-3,4-epoxide). The most mutagenic compound was anti-5-MeC-1,2-diol-3,4-epoxide, followed by syn-5-MeC-1,2-diol-3,4-epoxide. At the same doses, neither of the 6-MeC-1,2-diol-3,4-epoxides was mutagenic. These results demonstrate the enhancing effect on mutagenicity of a methyl group in the same bay region as the epoxide ring of a diol epoxide.

Carcinogens↗
PubMed1986

Effects of 6-nitro substitution on 5-methylchrysene tumorigenicity, mutagenicity and metabolism.

6-Nitro-5-methylchrysene was prepared by nitration of 5-methylchrysene and the mutagenic and tumorigenic activities of the two compounds were compared. Whereas 5-methylchrysene was a strong tumor initiator on mouse skin, no tumors were observed in the mice treated with 6-nitro-5-methylchrysene. In Salmonella typhimurium TA100, both compounds were mutagenic in the presence, but not in the absence, of rat liver 9000 g supernatant. The major metabolite of 6-nitro-5-methylchrysene in rat liver in vitro was trans-1,2-dihydro-1,2-dihydroxy-6-nitro-5-methylchrysene. In view of the ready conversion of 6-nitro-5-methylchrysene to a 1,2-dihydrodiol, its apparent lack of tumorigenicity in mouse skin was intriguing.

Animals↗
PubMed1986

Contrast, coagulation, and fibrinolysis.

Some adverse clinical effects of intravascular radiologic contrast agents have been attributed to their interference with the normal hemostatic processes. This study compares the effects of the low osmolality agents with those of the conventional agents by in vitro studies of platelet function, fibrin formation, and fibrinolytic activation. In various degrees, all the contrast agents studied inhibit platelet aggregation and fibrin formation but show virtually no direct activation of fibrinolysis. The new low osmolality agents generally show lesser inhibitory effects on the hemostatic mechanisms. Some clinical implications are discussed.

Blood Coagulation↗
PubMed1985

Mutagenicity and tumor initiating activity of methylated benzo[k] fluoranthenes.

The mutagenic activities toward Salmonella typhimurium TA100 and tumor initiating activities on mouse skin of the polynuclear aromatic hydrocarbons benzo[k]fluoranthene (BkF),2-methylBkF,8-methylBkF,9-methyl-BkF and 7,12-dimethylBkF were compared. BkF and 2-methylBkF were the most mutagenic of the compounds tested and had comparable activity; they were more active than 7,12-dimethylBkF. 8-MethylBkF and 9-methylBkF were not mutagenic. BkF and the methylated BkFs had similar tumor initiating activities on mouse skin. The results suggest that 8,9-dihydro-8,9-epoxy-BkF might be involved in the metabolic activation of BkF to a mutagen, but do not indicate which metabolite may be involved in BkF tumorigenesis.

Animals↗
PubMed1985

Mutagenicity and tumor initiating activity of methylated benzo[b]fluoranthenes.

The mutagenicity toward S. typhimurium TA 100 and tumor initiating activity on mouse skin of benzo[b]fluoranthene (BbF), 1-methylbenzo[b]fluoranthene (1-MeBbF), 3-MeBbF, 7-MeBbF, 8-MeBbF, 9-MeBbF, 12-MeBbF, 5,6-dimethylbenzo[b]fluoranthene (5,6-diMeBbF) and 1,3-diMeBbF were assayed. Dose-dependent mutagenic activity was observed for BbF, 3-MeBbF, and 1,3-diMeBbF; the other compounds were inactive at the doses tested. 3-MeBbF and 1,3-diMeBbF were strong tumor initiators, with activity greater than that of BbF. All the other compounds were less tumorigenic than BbF. The results suggest that the structural features favoring tumorigenicity of methylated non-alternant polynuclear aromatic hydrocarbons such as BbF are different from those favoring tumorigenicity of methylated alternant polynuclear aromatic hydrocarbons such as benzo[a]pyrene, chrysene and benz[a]anthracene.

Animals↗
PubMed1985

Tumorigenicity of 5-methylchrysene dihydrodiols and dihydrodiol epoxides in newborn mice and on mouse skin.

5-Methylchrysene, (+/-)-trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene, (+/-)-trans-7,8-dihydro-7,8-dihydroxy-5-methylchrysene, (+/-)-trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (anti-DE-I), (+/-)-trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (syn-DE-I), and (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (anti-DE-II) were tested for tumorigenicity in newborn mice and for tumor-initiating activity on mouse skin. In newborn mice, a total dose of 56 nmol of anti-DE-I induced 4.6 lung tumors/mouse and 1.2 liver tumors/mouse. These incidences were significantly higher than observed for any of the other metabolites, tested at equimolar doses. The results indicate that anti-DE-I, but not syn-DE-I or anti-DE-II, is a major ultimate carcinogen of 5-methylchrysene in the newborn mouse. Anti-DE-I was also more tumorigenic than anti-DE-II on mouse skin, inducing 4.4 tumors/mouse after an initiating dose of 100 nmol, compared to zero tumors per mouse induced by anti-DE-II. However, anti-DE-I was less tumorigenic on mouse skin than was its metabolic precursor, trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene or its parent hydrocarbon, 5-methylchrysene.

Animals↗
PubMed1985

Rates of hydrolysis and extents of DNA binding of 5-methylchrysene dihydrodiol epoxides.

The rates of hydrolysis in the absence and presence of native and denatured DNA, and the extents of DNA binding of five dihydrodiol epoxides derived from 5-methylchrysene (5-MeC) and chrysene have been determined. The compounds studied were: trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC; trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-Mec; trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC; trans-7,8-dihydroxy-syn-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC; and trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene. In the absence of DNA, at pH 7 and 37 degrees C half-lives of trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC and trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC were similar, t 1/2 = 62 and 59 min, while trans-7,8-dihydroxy-syn-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC hydrolyzed faster than trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC, t 1/2 = 5.4 versus 17.5 min; trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene had the slowest rate of hydrolysis, t 1/2 = 104 min. Studies of the effects of native and denatured DNA on the rates of hydrolysis of the dihydrodiol epoxides indicated that native DNA remarkably accelerated these rates for all dihydrodiol epoxides, but the degree of acceleration varied for the different dihydrodiol epoxides. The acceleration of hydrolytic rates by native DNA relative to that by denatured DNA was correlated with the covalent binding of these dihydrodiol epoxides with DNA in vitro. The catalytic effect of DNA in enhancing the rates of hydrolysis of dihydrodiol epoxides and the relative extents of covalent binding of the dihydrodiol epoxides to DNA were in the following order: trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC greater than trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC greater than trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene greater than trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC greater than trans-7,8-dihydroxy-syn-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC. The results of this study suggest that physical interactions with DNA are important in determining the relative extents of binding of these dihydrodiol epoxides to DNA in vitro.

Chromatography, High Pressure Liquid↗
PubMed1985

Comparative metabolic activation in mouse skin of the weak carcinogen 6-methylchrysene and the strong carcinogen 5-methylchrysene.

We compared the metabolic activation in mouse skin of the weak carcinogen 6-methylchrysene, which lacks a bay region methyl group, and the strong carcinogen 5-methylchrysene, which has a bay region methyl group. Metabolites of 6-methyl-chrysene were prepared using liver homogenates and were identified by their spectral properties and by comparison to synthetic standards as dihydrodiols, hydroxymethyl derivatives, and phenols; their relative levels of formation in liver homogenates from rats and mice were dependent on inducer pretreatment. In mouse skin in vivo, the major metabolite of 6-methyl-chrysene was trans-1,2-dihydro-1,2-dihydroxy-6-methylchrysene (6-MeC-1,2-diol), the precursor to a bay region dihydrodiol epoxide. Its concentration was greater than that of trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene (5-MeC-1,2-diol) formed in mouse skin from 5-methylchrysene. Since 5-MeC-1,2-diol has been identified as a major proximate carcinogen of 5-methylchrysene, the further metabolism and tumorigenicity of 5-MeC-1,2-diol and 6-MeC-1,2-diol were compared. Both dihydrodiols were converted to 1,2,3,4-tetraols and to 1,2-dihydroxy metabolites to similar extents in mouse skin. However, 5-MeC-1,2-diol was significantly more active than was 6-MeC-1,2-diol as a tumor initiator on mouse skin. The formation of DNA adducts in mouse skin from 5-methylchrysene and 6-methylchrysene was compared. Both hydrocarbons gave qualitatively similar adduct patterns, but the formation of dihydrodiol epoxide type adducts was 1/20 as great from 6-methylchrysene as from 5-methylchrysene. The results of this study indicate that the weak tumorigenicity of 6-methylchrysene compared to that of 5-methylchrysene is not due to differing rates of formation or further metabolism of their 1,2-dihydrodiols but is a likely consequence of the lower activity of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-methylchrysene compared to 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene; the unique structural feature of the latter is the presence of a methyl group and an epoxide ring in the same bay region.

Animals↗
PubMed1984

Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats.

Tobacco and tobacco smoke contain relatively high amounts of four tobacco-specific N-nitrosamines. Of these, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosoanatabine (NAT) were bioassayed at three dose levels by subcutaneous injections into male and female F344 rats in 60 subdoses amounting in total to 9,3, and 1 mmol/kg. Compared with the solvent control group (trioctanoin), both NNN and NNK induced significant numbers of tumors of the nasal cavity (P less than 0.01) at all three dose levels in both male and female rats. Significant numbers of tumors were also induced by NNK in the lung at all three dose levels and in the liver at the highest dose level (P less than 0.05). In addition to nasal tumors NNN also induced esophageal tumors at a significant rate in male rats at the high and medium dose levels and in female rats at the high level (P less than 0.05); NAT was inactive at the three doses tested. Bioassays at lower dose levels as well as biochemical studies are strongly indicated for NNN and NNK since these nitrosamines occur in relatively high amounts in both chewing tobacco and tobacco smoke.

Animals↗