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S Amin

Publications and source records attributed to S Amin.

At least 199 records · Page 11Linked to original sources
PubMed1984

The bay-region geometry of some 5-methylchrysenes: steric effects in 5,6- and 5,12-dimethylchrysenes.

The presence of a bay-region methyl group in carcinogenic polycyclic aromatic hydrocarbons leads to considerable distortion in the molecule. This is illustrated in the structures, obtained by X-ray diffraction techniques, of 5,12- and 5,6-dimethylchrysene. The molecular distortions result from steric requirements, such as that the minimum H...H distance is 1.8 A and the minimum C...C distance is 2.90 A; distortions to accommodate these requirements may be both in-plane (by increasing the angles at carbon atoms in the bay-region from 120 degrees to approximately 124 degrees) and out-of-plane by torsion about certain bonds in the bay-region. It is shown that more in-plane distortions are found for 5-methylchrysene derivatives than for methylbenz[a]anthracene derivatives and this, it is suggested, results from the nature of the flexibility of the chrysene compared with the benz[a]anthracene fragment at the bay-region.

Carcinogens↗
PubMed1984

Identification of the major adducts formed by reaction of 5-methylchrysene anti-dihydrodiol-epoxides with DNA in vitro.

5-Methylchrysene is metabolically converted to the bay-region dihydrodiol-epoxides, trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I), in which the methyl group and the epoxide ring are in the same bay region, and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II). Previous studies have indicated that DE-I is more important in 5-methylchrysene carcinogenesis than is DE-II. Both DE-I and DE-II were individually reacted with calf thymus DNA in vitro. The DNA was enzymatically hydrolyzed to deoxyribonucleosides, and the modified deoxyribonucleosides were separated by chromatography on Sephadex LH-20 and analyzed by high-performance liquid chromatography. One major adduct and seven minor adducts were formed from each dihydrodiol-epoxide. The major adduct was, in each case, characterized by its pH-dependent partition coefficient, stability to base, mass spectrum, ultraviolet spectrum, and nuclear magnetic resonance spectrum as a deoxyguanosine derivative resulting from addition of the exocyclic amino group of deoxyguanosine to the benzylic carbon of the epoxide ring of the dihydrodiol-epoxide. The results of this study show that the major DNA adducts formed from 5-methylchrysene via DE-I and DE-II are structurally similar.

Animals↗
PubMed1984

Inhibition by a peri-fluorine atom of 1,2-dihydrodiol formation as a basis for the lower tumorigenicity of 12-fluoro-5-methylchrysene than of 5-methylchrysene.

12-Fluoro-5-methylchrysene, which has a fluorine atom at a peri position, is less carcinogenic toward mouse skin than is 5-methylchrysene. To determine the basis for this observation, we identified metabolites of 12-fluoro-5-methylchrysene formed by rat liver in vitro, and used these as standards to study the metabolism of [3H]-12-fluoro-5-methylchrysene in mouse liver in vitro and in mouse epidermis in vivo. Metabolites were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra, by comparison to synthetic standards, and by chemical transformations. Dihydrodiols, phenols, and hydroxymethyl derivatives of 12-fluoro-5-methylchrysene were characterized. The extents of formation of 1,2-dihydro-1,2-dihydroxy-12-fluoro-5-methylchrysene and 7,8-dihydro-7,8-dihydroxy-12-fluoro-5-methylchrysene in mouse liver in vitro were strongly influenced by pretreatment with 3-methylcholanthrene, but the ratio of 1,2-dihydrodiol to 7,8-dihydrodiol was lower than in the metabolism of 5-methylchrysene carried out under identical conditions. The major metabolites of [3H]-12-fluoro-5-methylchrysene formed in mouse epidermis, 0.33 to 4 hr after topical application, were 7,8-dihydro-7,8-dihydroxy-12-fluoro-5-methylchrysene and 7-hydroxy-12-fluoro-5-methylchrysene. The ratio of 7,8-dihydro-7,8-dihydroxy-12-fluoro-5-methylchrysene to 1,2-dihydro-1,2-dihydroxy-12-fluoro-5-methylchrysene in mouse epidermis, 2 hr after application of [3H]-12-fluoro-5-methylchrysene, was 68:1, compared to 1:1 for the corresponding dihydrodiols of 5-methylchrysene. These results show that fluorine substitution at the 12-peri position of 5-methylchrysene inhibits formation of the 1,2-dihydrodiol in the adjacent ring. Since the 1,2-dihydrodiol is a major proximate carcinogen of 5-methylchrysene, the results provide an explanation for the relatively low carcinogenicity of 12-fluoro-5-methylchrysene.

Animals↗
PubMed1982

Tumour initiating activity of dihydrodiols of benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene.

The tumor initiating activities on mouse skin of benzo[b]fluoranthene, (B[b]F), benzo[j]fluoranthene (B[j]F), benzo[k]fluoranthene (B[k]F] and three of their dihydrodiols, 9,10-dihydro-9,10-dihydroxybenzo[b]fluoranthene (B[b]F-9,10-diol), 9,10-dihydro-9,10-dihydroxybenzo[j]fluoranthene (B[j]F-9,10-diol), and 8,9-dihydro-8,9-dihydroxybenzo[k]fluoranthene (B[k]F-8,9-diol) were evaluated. Among the parent hydrocarbons, B[b]F was the most potent tumor initiator, with activity greater than that of B[j]F but less than that of benzo[a]pyrene. B[k]F also showed tumor initiating activity, in contrast to its lack of complete carcinogenic activity on mouse skin. B[b]F-9,10-diol, which can form a bay region dihydrodiol epoxide, was as active as B[b]F. B[j]F-9,10-diol, which would form its dihydrodiol epoxide in a four sided pseudo-bay region, was less active than B[j]F. B[k]F-8,9-diol was inactive. These results, together with parallel metabolic studies, suggest that the formation of bay region dihydrodiol epoxides may not be the major activation mechanism in benzofluoranthene tumorigenesis.

Animals↗
PubMed1982

Identification of metabolites of 5,11-dimethylchrysene and 5,12-dimethylchrysene and the influence of a peri-methyl group on their formation.

We investigated the in vitro metabolism by mouse and rat liver 9000 x g supernatant of the strong tumor initiator, 5,11-dimethylchrysene (5,11-diMeC) and its inactive analogue, 5,12-dimethylchrysene (5,12-diMeC). Ethyl acetate soluble metabolites were separated by h.p.l.c. and identified by their u.v. and m.s. and by comparison to selected synthetic reference standards. Both compounds were converted to dihydrodiols, chrysenols, hydroxymethylchrysenes, and hydroxymethylchrysenols. The peri 12-methyl group of 5,12-diMeC strongly inhibited metabolism at the adjacent 1,2-positions. Thus, the ratio of 7-hydroxy-5,12-diMeC to 1-hydroxy-5,12-diMeC was approximately 100 to 1 when 5,12-diMeC was metabolized by liver supernatants from 3-methylcholanthrene pretreated mice and rats. In addition, 7,8-dihydro-7,8-dihydroxy-5,12-diMeC was preferentially formed over 1,2-dihydro-1,2-dihydroxy-5,12-diMeC by liver supernatants from control, 3-methylcholanthrene pretreated, and Aroclor pretreated animals. In contrast, the presence of a methyl group at the 11 position of 5,11-diMeC did not inhibit formation of 1-hydroxy-5,11-diMeC or 1,2-dihydro-1,2-dihydroxy-5,11-diMeC. Since 1,2-dihydro-1,2-dihydroxy metabolites of 5-methylchrysene derivatives are potential proximate tumorigens, these results may provide a basis for the higher tumorigenicity of 5,11-diMeC than of 5,12-diMeC.

Animals↗
PubMed1982

Identification of metabolites of benzo[b]fluoranthene.

The metabolism by rat liver 9000 x g supernatant of the environmental carcinogen benzo[b]fluoranthene was investigated. The major metabolites were identified, by comparison to synthetic samples, as 5- and 6-hydroxybenzo[b]fluoranthene and 4- and 7-hydroxybenzo[b]fluoranthene. The principal dihydrodiol metabolite formed under these conditions was trans-11,12-dihydro-11,12-dihydroxybenzo[b]fluoranthene, which was identified by comparison to the synthetic compound. 1,2-Dihydro-1,2-dihydroxybenzo[b]fluoranthene was identified, by its mass spectrum and by comparison if its u.v. spectrum to that of a synthetic model compound, 11-ethylidene-11H-benzo[b]fluorene. No evidence was obtained for the formation of 7b,8-dihydro-7,8-dihydroxybenzo[b]fluoranthene or trans-9,10-dihydro-9,10-dihydroxybenzo[b]fluoranthene. The latter would be the precursor to a bay region dihydrodiol epoxide of benzo[b]fluoranthene.

Animals↗
PubMed1981

Three or four copies of a dicentric 17q isochromosome in an acute myeloproliferative disorder.

The majority of metaphases in the bone marrow of a male patient aged 72 with a rapidly evolving aleukemic erythremic myelosis had 48 chromosomes with three copies, or 49 chromosomes with four copies, of an i(17q), which was seen to be dicentric in C-banded and Giemsa-11-banded preparations. There was also loss of a chromosome No. 5 and the addition of a chromosome resembling a No. 22. The presence of multiple copies of the isochromosome is postulated to be related to the acuteness of the condition.

Acute Disease↗
PubMed1981

Effects of fluorine substitution on the tumor initiating activity and metabolism of 5-hydroxymethylchrysene, a tumorigenic metabolite of 5-methylchrysene.

The tumor initiating activity on mouse skin of 5-hydroxymethylchrysene (5-HOMeC), a major metabolite of the carcinogen, 5-methylchrysene (5-MeC), was investigated. After an initiating dose of 30 microgram, with promotion by tetradecanoylphorbol acetate, 5-HOMeC induced skin tumors in 90% of the animals, with 9.5 tumors/mouse, 5-MeC gave a 75% incidence of skin tumors with 6.2 tumors/mouse. The tumorigenic activities after a 10 microgram initiating dose were; 5-HOMeC, 45% skin tumor-bearing animals and 2.6 tumors/-mouse; 5-MeC, 55% skin tumor-bearing animals and 5.6 tumors/mouse. In contrast, 6-hydroxy-methylchrysene was inactive. To investigate the mechanism of activation of 5-HOMeC, 3-fluoro-5-hydroxymethylchrysene (3-F-5-HOMeC) and 7-fluoro-5-hydroxymethylchrysene (7-F-5-HOMeC) were prepared and assayed for tumor initiating activity at a dose of 30 microgram. 7-F-5-HOMeC gave 95% tumor-bearing animals and 7.9 tumors/animal whereas 3-F-5-HOMeC gave only 5% tumor-bearing animals and 0.1 s/animal. The inhibition of tumorigenicity by substitution of fluorine at the 3-position, but not the 7-position of 5-HOMeC is strictly analogous to results obtained previously with 5-MeC and suggests a similar mechanism of activation for both compounds. The metabolites formed upon incubation of 5-HOMeC with cofactors and the 9000 x g supernatant from Aroclor pretreated rats were separated by h.p.l.c. The 1,2-dihydrodiol and 7,8-dihydrodiol of 5-HOMeC were identified. The major phenolic metabolite was identified as 1-hydroxy-5-hydroxymethylchrysene. In the in vitro metabolism of 7-F-5-HOMeC under the same conditions, we identified the 1,2-dihydrodiol but not the 7,8-dihydrodiol. In the metabolism of 3-F-5-HOMeC, oxidation in the 1-4 ring was inhibited relative to that observed in the metabolism of 5-HOMeC. These results suggest that 5-HOMeC is activated primarily through formation of its 1,2-dihydrodiol.

Animals↗
PubMed1981

Effects of gonadotrophin treatment in vivo on testicular function in immature rhesus monkeys (Macaca mulatta).

Changes in testicular histology and concentrations of testosterone and oestradiol 17 beta in testicular tissue and plasma have been studied following administration of gonadotrophins (oFSH, oLH, hCG and PMSG) to immature male monkeys. Treatment with FSH (1 mg/day) or PMSG (100 IU/day) for five days, induced a marked enlargement of the seminiferous tubules and increase in the Sertoli cell cytoplasm. Injections of LH (1 mg/daily) or hCG (100 IU/daily) administered similarly, failed to produce hypertrophy of the Sertoli cell. In LH, hCG and PMSG stimulated testes morphologically differentiated interstitial cells could be recognized. FSH did not produce any detectable effect on the intertubular tissue. A significant increase in testicular and plasma testosterone levels was observed with LH, hCG and PMSG. FSH was shown to be much less effective in stimulating androgenesis. An increase in testicular oestradiol production over that of controls, was observed in FSH and PMSG treated monkeys but not in animals treated with LH or hCG.

Animals↗
PubMed1980

Long-term clearance of [57Co]cyanocobalamin in vegans and pernicious anaemia.

1. Whole-body counting has been used to monitor the clearance of [57Co]cyanocobalamin in normal subjects, vegans and patients with pernicious anaemia. After oral administration of 57Co-labelled cyanocobalamin (1 microgram/1 muCi), subjects were counted for radioactivity monthly for a maximum period of 1 year. 2. The results obtained were consistent with a monoexponential clearance model and a least squares fit showed that there was no significant difference between the mean clearance rates for the vegans and normal subjects. 3. The patients with pernicious anaemia cleared the vitamin significantly more quickly than the normal control subjects. 4. This may be due to failure to reabsorb biliary vitamin B12 in pernicious anaemia because of the absence of intrinsic factor.

Adolescent↗
PubMed1980

Selenium in premature infants.

Premature infants have a lower selenium concentration in serum than full-term infants and children. The selenium concentration goes down quickly in infants treated for respiratory distress syndrome without supplementation. One premature infant with bronchopulmonary dysplasia had persistently low concentrations of selenium. Vitamin E supplements did not affect the serum selenium concentration in healthy premature infants. Supplementation with 3 microgram/kg of selenium in parenteral fluids prevented the fall in the concentration seen in other infants not supplemented. Premature infants and especially those treated with oxygen may warrant selenium supplementation to the parenteral nutrition solution. Vitamin E supplements alone are apparently not sufficient to prevent selenium deficiency and potential oxygen toxicity.

Adolescent↗
PubMed1980

Identification of mutagenic dihydrodiols as metabolites of benzo(j)fluoranthene and benzo(k)fluoranthene.

The metabolism of the environmental agents benzo(j)-fluoranthene and benzo(k)fluoranthene was investigated using supernatants from the livers of Aroclor 1254-pretreated rats, which are effective in activating benzo(j)fluoranthene and benzo(k)fluoranthene to metabolites mutagenic toward Salmonella typhimurium TA 100. Six bands of metabolites of benzo(j)fluoranthene were separated by high-pressure liquid chromatography, and each band was tested for mutagenicity toward S. typhimurium TA 100 with activation. The major mutagenic band contained two dihydrodiols, one of which was identified as 9,10-dihydro-9, 10-dihydroxybenzo(j)fluoranthene by comparison to a synthetic reference standard. 9,10-Dihydro-9,10-dihydroxybenzo(j)fluoranthene was mutagenic toward S. typhimurium TA 100 with activation, presumably as a result of conversion to the corresponding dihydrodiol-epoxide. The major dihydrodiol metabolite of benzo(k)fluoranthene was identified, by comparison to a synthetic standard, as 8,9-dihydro-8,9-dihydroxybenzo(k)fluoranthene. This dihydrodiol, which could also be converted to a dihydrodiol-epoxide, was mutagenic toward S. typhimurium TA 100 with activation. The results of this study indicate that metabolism to dihydrodiols is one pathway in the activation of benzo(j)fluoranthene and benzo(k)fluoranthene to ultimate mutagens for S. typhimurium TA 100.

Animals↗
PubMed1979

Effect of growth hormone on lymphocyte respiration and growth rate of children.

Oxygen consumption by circulating lymphocytes of children with isolated growth hormone deficiency was studied before and 6 mo after the start of growth hormone therapy. A plot of percent change in respiration (oxygen consumed per mg protein or microgram DNA) against height gain during the therapy showed a linear association (correlation coefficient 0.667--0.756).

Adolescent↗
PubMed1979

Tumor initiating activity of 5,11-dimethylchrysene and the structural requirements favoring carcinogenicity of methylated polynuclear aromatic hydrocarbons.

The tumor initiating activities of 5,11-dimethylchrysene and 5-methylchrysene on mouse skin were compared. After initiating doses of 30 microgram or 10 microgram, with promotion by 3 times weekly applications of tetradecanoylphorbol acetate, both compounds were highly tumorigenic, inducing tumors in 70--85% of the treated animals. Since 5,12-dimethylchrysene had previously been shown to be only a weak tumor initiator, these results support the generalization that the structural requirements favoring carcinogenicity among the methylated chrysenes and other polynuclear aromatic hydrocarbons (PAH) are a bay region methyl group and a free peri position, both adjacent to an unsubstituted angular ring.

Animals↗
PubMed1979

Synthesis and mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized derivatives of 5-methylchrysene.

A series of compounds structurally related to the carcinogen and mutagen 5-methylchrysene (1) was synthesized and tested for mutagenicity toward S. typhimurium TA 100. The compounds prepared were 5,11-dimethylchrysene (2), 5-(hydroxymethyl)chrysene (3), 5-(acetoxymethyl)chrysene (4), 5-carbomethoxychrysene (5), 5-(hydroxymethyl)-1,2,3,4-tetrahydrochrysene (6), 5-carbomethoxy-1,2,3,4-tetrahydrochrysene (7), and 5H-chryseno[4,5-bcd]pyran-5-one (31). When tested in the presence of rat liver homogenate, 1 and 2 were active while 3--7 were less mutagenic than 1; 31 was highly mutagenic. The mutagenicity of 1 and 2 contrasts with the low activity of 5,12-dimethylchrysene, which supports the generalization that the structural requirements favoring activity are a bay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring. The low activity of 3--7 indicates that methyl oxidation is not an important activation process for 1. This agrees with previous studies in which the major proximate mutagen and carcinogen of 1 was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene.

Animals↗
PubMed1978

1,2-dihydro-1,2-dihydroxy-5-methylchrysene, a major activated metabolite of the environmental carcinogen 5-methylchrysene.

The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurium. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activiation. Significant mutagenic activity was observed primarily in peak E and to a lesser extent in peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hydroxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.

Animals↗