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Biomedical subjects

S Amin

Publications and source records attributed to S Amin.

At least 163 records · Page 9Linked to original sources
PubMed1991

Comparative DNA binding of polynuclear aromatic hydrocarbons and their dihydrodiol and bay region diolepoxide metabolites in newborn mouse lung and liver.

Bay region diolepoxides of polynuclear aromatic hydrocarbons (PAHs) generally are more tumorigenic than their parent PAHs in newborn mice. This contrasts to the results obtained in mouse skin, in which the same diolepoxides are frequently less tumorigenic than their parents. In order to evaluate mechanism(s) responsible for this behavior we have investigated the binding of metabolites of [3H]benzo[a]pyrene (B[a]), [3H]5- and [3H6]6-methyl-chrysene (5-MeC and 6-MeC) and their corresponding dihydrodiols and bay region diolepoxides to pulmonary and hepatic DNA in male and female newborn mice and compared the results with their tumorigenic activities. Groups of 1 day old mice were treated with 0.4 or 4 nmol of the appropriate compounds in DMSO by i.p. injection. HPLC analysis of DNA hydrolysates obtained 24 h after treatment indicated that levels of diolepoxide-DNA adducts following treatment with (+-)-[3H]7,8-dihydroxy-7,8-dihydroB[a]P and (+-)-[3H]anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroB[a] P are 5- and 10-fold higher than those formed from [3H]B[a]P. The major products (70-80%) released upon enzymatic hydrolysis of DNA following treatment with [3H]B[a]P, [3H]5-MeC and [3H]6-MeC were unidentified polar compounds. Levels of these unknown products were lower and formation of diolepoxide--DNA adducts higher when test compounds were changed from parent PAHs to the corresponding dihydrodiols and diolepoxides. Comparison of these results with those of tumorigenesis studies indicates a correlation between formation of B[a]P-diolepoxide--DNA adducts and induction of tumors in newborn mouse lung, but not in liver. These observations are consistent with the high sensitivity of the newborn mouse lung towards the tumorigenic effects of bay region diolepoxides. Previous studies have demonstrated that 1R,2S-dihydroxy-3S,4R,epoxy, 1,2,3,4-tetrahydro-5-MeC (5-MeC-1R,2S-diol-3S,4R-epoxide) is a potent lung tumorigen while the corresponding diol-epoxide of 6-MeC had no effect in newborn mice. From the results of the present study, we estimate that at equimolar doses the formation of diolepoxide--DNA adducts from 5-MeC-1R,2S-diol-3S,4R-epoxide would be at least 20-fold greater than from the corresponding diolepoxide of 6-MeC in newborn mouse lung. Thus, the higher tumorigenic activity of 5-MeC-1R,2S-diol-3S,4R-epoxide compared to that of the corresponding diol epoxide of 6-MeC is partially due to its greater extent of DNA damage.

Animals↗
PubMed1991

Prevaccination serologic screening for measles in health care workers.

A model was developed from which the cost-effectiveness of prevaccination serologic screening for measles could be estimated, for any combination of antibody screening costs and prevalence of antibody to measles. This model was tested using sera obtained prospectively from 222 health care workers, including 181 born in or after 1957 who had no history of measles, no measles vaccine after 1980, and no documentation of immunity to measles. In addition, 41 subjects born before 1957 who had no history of measles were studied. A rapid, reliable, and inexpensive ($5 per test) commercial ELISA was used to test for antibodies to measles; its seroprevalence in the subject population was 86%. From the model, it was estimated that prevaccination serologic testing would be cost-effective if antibody screening cost less than or equal to $12.75 per test. In this subject population, prevaccination serologic screening for measles was cost-effective.

Adult↗
PubMed1991

Perceptual attitudes of a charitable organization: an investigative approach.

United Way of America is known nationwide for its services as a coordinator of local fund raising activities designed to meet the needs of the local community. Each United Way has many local agencies that depend upon the fund raising efforts of the organization for a significant amount of their budget. The United Way of Horry County (UWHC) operates in this manner, and over the years they have raised a significant amount of funds to support local service agencies. The UWHC is now attempting to examine possible changes by embarking upon a study designed to measure among the public the degree of awareness of United Way and the services which they provide. A sample survey was conducted and data were collected via telephone solicitation from individuals selected randomly throughout the market area of Horry County. The study identified the four most important services as: emergency assistance such as housing, fire, flood, etc., senior citizens, health care services, and drug and alcohol abuse. Furthermore, the study indicated that services which need to be added to this list include AIDS research, aid for homeless, mentally ill, and elderly.

Adolescent↗
PubMed1991

The impact of a public-health intervention on sex differentials in childhood mortality in rural Punjab, India.

This paper examines the effects of a public-health intervention program on sex differentials in health and mortality during childhood. Among the different health-service packages offered as part of the experimental design, those including nutritional services seem to have been more successful in reducing excess female mortality. The reason for this success appears to have been careful follow-up of undernourished children by project workers. The results also indicate that, consistent with earlier research, girls with surviving older sisters had higher mortality rates after their first month of life. Contrary to earlier research, however, boys with surviving older brothers also have higher mortality rates, at least between the ages of one and three years. We conclude that these effects for boys and girls cannot be attributed to problems associated with larger family size, since the number of older siblings of the opposite sex (regardless of survival status) does not generally appear to be related to children's chances of survival.

Child↗
PubMed1990

Comparative tumor initiating activities of cyclopentano and methyl derivatives of 5-methylchrysene and chrysene.

Previous studies showed that 5,6-dimethylchrysene (5,6-diMeC) and 5,7-diMec were significantly less tumorigenic than 5-methylchrysene (5-MeC). These results were unexpected based on the known mechanism of metabolic activation of 5-MeC and indicated the presence of critical steric requirements for tumorigenicity at the 6 and 7 positions of 5-MeC. In this study, the structure activity relationships were further extended by comparing the tumor-initiating activities on mouse skin of 5-MeC, 6,7-cyclopentano-5-MeC, 5,6-diMeC, 6,7-diMeC, 5,7-diMeC, chrysene and 6,7-cyclopentanochrysene. 5-MeC was the most tumorigenic compound, with activity significantly higher than all other compounds tested. Among the other compounds. Only 5,6-diMeC was significantly tumorigenic. The results demonstrate that substitution of methyl or methylene groups at the 6 or 7 positions of 5-MeC leads to a significant reduction of tumor initiating activity.

Animals↗
PubMed1990

Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein.

The vitamin A derivative retinoic acid is known to be a potent agent for control of differentiation and proliferation of epithelial cells and to exert profound effects on pattern formation during embryogenesis. Its action at the molecular level appears to be mediated by two distinct classes of proteins: a family of nuclear receptors that regulates gene transcription in a ligand-dependent fashion and a small cellular retinoic acid-binding protein (CRABP) for which a precise function remains to be elucidated. In this report, we describe the identification (by molecular cloning of its cDNA) of an isoform of CRABP, referred to as CRABP-II, expressed at high levels during mouse embryogenesis and in adult skin. We also show that CRABP-II mRNA levels are induced by at least 50-fold upon treatment of F9 teratocarcinoma cells with retinoic acid. The up-regulation of the gene encoding CRABP-II by its ligand suggests that CRABP-II might be involved in a feedback regulatory role in the mechanism of action of retinoic acid on cellular differentiation.

Amino Acid Sequence↗
PubMed1990

Differences in conformations of covalent adducts derived from the binding of 5- and 6-methylchrysene diol epoxide stereoisomers to DNA.

The conformations of adducts derived from the covalent binding of four different isomeric diol epoxide derivatives of 5- or 6-methylchrysene to native double-stranded calf thymus DNA were studied by linear dichroism techniques. Out of four isomers investigated here, only the R,S,S,R enantiomer of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene, (+)-5-MeCDE, is highly tumorigenic and mutagenic toward Salmonella typhimurium TA100; the S,R,R,S enantiomer, (-)-5-MeCDE, and the corresponding R,S,S,R and S,R,R,S enantiomers of anti-1,2,-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-methylchrysene are non-tumorigenic and much less mutagenic than (+)-5-MeCDE. [Melikian et al., (1988) Cancer Res., 48, 1781-1787] Only the DNA adducts derived from the binding of (+)-5-MeCDE are characterized by a pronounced positive linear dichroism signal at 308 nm due to the phenanthrenyl residue which is tilted at an angle of 45-48 degrees with respect to the average orientations of the axes of unoriented DNA segments. The phenanthrenyl residues derived from the covalent binding to DNA of the other three inactive or less active isomers appear to be unoriented. The defined orientation of the covalently bound phenanthrenyl residues derived from (+)-5-MeCDE corresponds to adduct conformations which are similar to those obtained from the binding of the highly tumorigenic trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene stereoisomer and other highly active bay-region diol epoxide derivatives to DNA. These findings provide further evidence that there is a correlation between DNA adduct conformation and biological activities for these series of polycyclic aromatic diol epoxide derivatives with R,S,S,R absolute configuration and which are known to bind predominantly to N2 of guanine.

Carcinogens↗
PubMed1990

Infant mortality and breastmilk supplementation in Bangladesh.

The effects of timing and type of breast-milk supplementation on infant mortality in Bangladesh are analyzed using a discrete time analog of a continuous time proportional hazards model. Data are from the Determinants of Natural Fertility Study conducted from 1975 to 1978 among some 2,000 women in Matlab thana. "The statistical analyses show that breastfeeding type at various stages of the child's life is a significant predictor of infant mortality, even when variables such as...mother's [age], education, religion and SES [socioeconomic status] are included in the model. The study shows that infants breastfed at birth have better probabilities of survival relative to those who are never breastfed or are given liquid supplements very early in life. This effect remains significant even when mother's nutrition at childbirth, which is used as a proxy for birth weight, is controlled."

Asia↗
PubMed1989

A study of tobacco carcinogenesis XLIV. Bioassay in A/J mice of some N-nitrosamines.

The evaluation of the tumorigenic activity in A/J mouse lung of certain tobacco N-nitrosamines, namely 3-(methylnitrosamino)propionic acid (NMPA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-4-(3-pyridyl)-butyric acid (iso-NNAC), had the following results (total dose in micromol per mouse/lung tumors per mouse): NMPA (200/7.1 +/- 2.9); NNK (2/15.7 +/- 4.1); iso-NNAC (200/0.24 +/- 0.43); saline control (0.2 +/- 0.4). The tumorigenic activity of NMPA was not surprising since its lower homologue, N-nitrososarcosine, as well as its higher homologue, 4-(methylnitrosamino)-butyric acid, are known carcinogens. The high tumorigenic activity of NNK in strain A/J mice confirms earlier findings as to its carcinogenic potency in rats and hamsters. The lack of tumorigenic activity of iso-NNAC supports the observation that the pyridyl rest adjacent to the nitrosamino group inhibits the activity of some tobacco-specific N-nitrosamines (TSNA). Iso-NNAC is most likely formed endogenously from the nicotine metabolites cotinine and 4-(methylamino)-4-(3-pyridyl)butyric acid.

Animals↗
PubMed1989

Evaluation of the transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice.

The transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was assessed in three strains of mice: A/J; C3H/He x C57BL/6 F1 (hereafter called C3B6F1); and Swiss outbred [Cr:NIH(S)]. NNK (100 mg/kg) was administered i.p. on Days 14, 16, and 18 of gestation to A/J and C3H/He mice and on Days 15, 17 and 19 of gestation to the Swiss mice. The effects of postnatal treatment with tumor-promoting agents, including 0.05% sodium barbital in the drinking water until death or a single dose of Aroclor 1254 (a mixture of polychlorinated biphenyls, PCB) given on Postnatal Day 8 or 56, were also examined. Progeny were sacrificed at age 24 wk (A/J) or 72 wk (C3B6F1 and Swiss). Significant incidences of tumors occurred in the lungs of strain A/J progeny and in the livers of male C3B6F1 and Swiss progeny. Lung tumor incidence was 8 of 34 (24%) in the female offspring of the A/J mice treated with NNK, compared with 1 of 39 (3%) in controls (P less than 0.05). A 2-fold difference in lung tumor incidence in male offspring of NNK-treated (4 of 23, 13%) versus control (3 of 48, 6%) A/J mice was not of statistical significance. However, the incidence of lung tumors in NNK-exposed progeny A/J mice in both sexes combined (12 of 66, 18%) was also significantly greater than in controls (4 of 87, 5%). The incidence of liver tumors in the male C3B6F1 mice exposed transplacentally to NNK was 12 of 30 (40%) compared to 8 of 46 (17%) in controls (P less than 0.05). No effects of postnatal sodium barbital or PCB were observed on transplacental NNK tumorigenicity in C3B6F1 mice. The combined incidence of liver carcinoma in male mice in all NNK-treated groups (13 of 141, 9%) was significantly greater (P less than 0.05) than in controls (5 of 144, 3%). In male Swiss mice exposed transplacentally to NNK, the incidence of liver tumors was 3 of 57 (5%) compared to 0 of 35 controls, and postnatal treatment with PCB on Day 56 caused a significant increase (5 of 26, 19%) (P less than 0.05) in the incidence of NNK-induced liver tumors. The combined incidence of liver tumors in the male offspring of the Swiss mice treated with NNK, with or without PCB, was 8 of 83 (10%) which was significantly greater (P less than 0.05) than in controls (0 of 66).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Effects of fluorine substitution on the DNA binding and tumorigenicity of benzo[b]fluoranthene in mouse epidermis.

The effects of fluorine substitution on benzo[b]fluoranthene (B[b]F) DNA adduct formation and tumorigenicity in mouse epidermis were investigated. Fluoro derivatives studied included 1-, 6-, 7-, 8-, 9- and 11-fluoroB[b]F as well as 1,9- and 6,9-difluoroB[b]F. Each compound was applied topically to mice and hydrocarbon/DNA adduct formation was assessed using the 32P-post-labelling technique. All of the fluorinated compounds bound to DNA to a lesser extent than B[b]F. Among the fluorinated compounds, the greatest binding was observed for 8-fluoroB[b]F. Lowest levels of hydrocarbon/DNA adduct formation from the fluoro derivatives were observed for 1-, 7-, 11- and 6,9-difluoroB[b]F. The tumor-initiating activities on mouse skin of 7-, 9- and 11-fluoroB[b]F were determined. All three compounds were significantly less tumorigenic than B[b]F. The results of this study are discussed with respect to possible mechanisms of metabolic activation of B[b]F.

Animals↗
PubMed1989

Rapid single-dose model for lung tumor induction in A/J mice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the effect of diet.

This paper describes the development of a relatively rapid single-dose model for induction of lung adenomas in female A/J mice by the tobacco-specific nitrosamine 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK). Mice maintained on AIN-76A semi-synthetic diet were given a single i.p. dose of 2.5, 5 or 10 mumol NNK in saline and killed 3-7 months later. Maximum lung tumor induction, measured by lung tumors per mouse (tumor multiplicity), occurred in 3.5 months. There was no significant increase in tumor multiplicity between 3.5 and 7 months. Four months after treatment, numbers of lung tumors per mouse were 11.9 +/- 1.0 (10 mumol NNK), 3.6 +/- 0.4 (5 mumol), 0.9 +/- 0.4 (2.5 mumol) and 0.07 +/- 0.1 (saline). Lung tumor multiplicity in mice treated with a single dose of 10 mumol NNK and maintained on AIN-76A diet was significantly higher (8.3 +/- 0.5) than in mice treated with NNK and maintained on NIH-07 diet (2.5 +/- 0.3). The results of this study establish a useful bioassay for identification of compounds that can modify NNK-induced lung tumorigenesis.

Adenoma↗
PubMed1989

Chromatographic conditions for separation of 32P-labeled phosphates of major polynuclear aromatic hydrocarbon--deoxyribonucleoside adducts.

The 3'-monophosphates of the major deoxyribonucleoside adducts of five representative polynuclear aromatic hydrocarbons (PAH)-benzo[a]pyrene, benz[a]anthracene, chrysene, 5-methylchrysene and 6-methylchrysene--were prepared by reaction with DNA of the appropriate bay-region diol epoxides followed by enzymatic hydrolysis and HPLC purification. These standards were converted to 3',[32P]-5'-bisphosphates as in the Randerath 32P-postlabeling assay. TLC and HPLC systems for their separation are described. HPLC conditions for separation of the corresponding 3'- and 5'-monophosphates are also reported. These data will be useful for determining whether unknown DNA adducts detected by the 32P-postlabeling assay may have resulted from reactions of DNA with PAH diol epoxides.

DNA↗
PubMed1989

The effects of bay-region methyl substitution on 6-nitrochrysene mutagenicity in Salmonella typhimurium and tumorigenicity in newborn mice.

The mutagenic activities in Salmonella typhimurium and tumorigenic activities in newborn mice of 6-nitrochrysene (6-NC), 5-methyl-6-nitrochrysene (5-Me-6-NC), 11-methyl-6-nitrochrysene (11-Me-6-NC) and 5-methylchrysene (5-MeC) were compared. In S. typhimurium TA100 in the absence of rat liver 9000 g supernatant, 11-Me-6-NC was the most active compound followed by 6-NC; 5-Me-6-NC and 5-MeC were inactive. In the assays conducted in the presence of rat liver 9000 g supernatant, the order of activity was 11-Me-6-NC greater than 6-NC greater than 5-Me-6-NC approximately 5-MeC. In S. typhimurium TA98 a similar trend was observed. For the tumorigenicity studies, groups of mice were treated with the appropriate compounds in DMSO by i.p. injections on the 1st, 8th and 15th day of life. At a dose of 100 nmol/mouse 6-NC induced significantly more lung tumors than 5-MeC, which in turn was more active than 11-Me-6-NC and 5-Me-6-NC. All compounds induced significant numbers of liver tumors in treated males compared to controls; the order of activity was the same as that observed for lung tumor induction. The results of this study clearly indicate that bay region methyl substitution can either inhibit (5-position) or enhance (11-position) the mutagenic activity of 6-NC. In contrast, bay region methyl substitution (5- and 11-positions) inhibited the tumorigenic activity of 6-NC in newborn mice. Since ring oxidation and nitroreduction are involved in the metabolic activation of 6-NC in newborn mice, bay region methyl substitution may either inhibit the nitroreduction pathway or hinder the formation of the appropriate bay region diol epoxide. Steric factors may be important in determining the tumorigenicity of methylated nitrochrysenes.

Animals↗
PubMed1988

Induction of lung and exocrine pancreas tumors in F344 rats by tobacco-specific and Areca-derived N-nitrosamines.

The tobacco-specific N-nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as well as the Areca-derived N-nitrosoguvacoline (NG) were assayed for carcinogenicity in male F344 rats by lifetime administration in the drinking water. Groups of 30 to 80 rats were treated with 0.5 ppm, 1.0 ppm, or 5.0 ppm of NNK; 5.0 ppm of NNAL, 20 ppm of NG, a mixture of 20 ppm of NG and 1 ppm of NNK, and water only in the control group. The approximate total doses of the nitrosamines (mmol/kg of body weight) in these groups were: NNK, 0.073, 0.17, and 0.68; NNAL, 0.69; NG, 4.1; NG and NNK, 4.1 and 0.17. As in previous assays in which NNK was tested by s.c. injection, the lung was its principle target organ. Lung tumor incidences in the 0.5-, 1.0-, and 5.0-ppm groups were nine of 80, 20 of 80, and 27 of 30 compared to six of 80 in the control rats. This trend was significant, P less than 0.005. Significant incidences of nasal cavity and liver tumors were observed only in the rats treated with 5.0 ppm of NNK. In contrast to the results of the s.c. bioassays of NNK, tumors of the exocrine pancreas were observed in five of 80 and nine of 80 rats treated with 0.5 and 1.0 ppm. This trend was significant, P less than 0.025. This is the first example of pancreatic tumor induction by a constituent of tobacco smoke. It is also the first finding of duct-like carcinomas in the rat pancreas, including one tumor containing epidermoid, keratin-generating tissue. NNAL, the major metabolite of NNK, induced lung tumors in 26 of 30 rats and pancreatic tumors in eight of 30 rats. It appears to be the proximate pancreatic carcinogen of NNK. NG induced pancreatic tumors in four of 30 rats, P less than 0.05. This finding requires confirmation. The mixture of NG and NNK induced lung tumors in eleven of 30 rats. There were no apparent synergistic interactions of NG and NNK. The observation of benign and malignant tumors of the lung and pancreas of rats treated with the tobacco-specific nitrosamines NNK and NNAL is discussed in respect to the causal association between cigarette smoking and cancer of the lung and pancreas.

Animals↗
PubMed1988

Reactivity with DNA bases and mutagenicity toward Salmonella typhimurium of methylchrysene diol epoxide enantiomers.

The reactions with DNA and mutagenic activities toward Salmonella typhimurium TA 100 of the R,S,S,R and S,R,R,S enantiomers of anti-1,2,-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (anti-5-MeC-1,2-diol-3,4-epoxide), anti-5-MeC-7,8-diol-9,10-epoxide, and anti-6-MeC-1,2-diol-3,4-epoxide were compared because among these compounds only the R,S,S,R enantiomer of anti-5-MeC-1,2-diol-3,4-epoxide is highly tumorigenic. The major products formed in the reaction of each racemic diol epoxide with DNA were two pairs of deoxyguanosine (dGuo) and deoxyadenosine (dAdo) adducts; one product in each pair was formed from the R,S,S,R enantiomer and the other from the S,R,R,S enantiomer of each racemic diol epoxide. Formation of products from R,S,S,R enantiomers exceeded formation of those from S,R,R,S enantiomers in each case. Among the R,S,S,R enantiomers, 5-MeC-1,2-diol-3,4-epoxide, which has a methyl group in the same bay region as the epoxide ring, was most reactive toward DNA, and in particular toward dGuo. The dGuo/dAdo adduct ratios were greater for the products formed from the R,S,S,R enantiomer compared to the S,R,R,S enantiomer of each diol epoxide. The dGuo/dAdo adduct ratios were also greater for the enantiomers of anti-5-MeC-1,2-diol-3,4-epoxide than for the enantiomers of either anti-5-MeC-7,8-diol-9,10-epoxide or anti-6-MeC-1,2-diol-3,4-epoxide. In S. typhimurium TA 100, the R,S,S,R enantiomer of anti-5-MeC-1,2-diol-3,4-epoxide was the most mutagenic compound (6700 revertants/nmol), followed by the R,S,S,R enantiomer of anti-5-MeC-7,8-diol-9,10-epoxide (1500 revertants/nmol). The other diol epoxide enantiomers were weakly active or inactive at the doses tested. The results of this study demonstrate that both the absolute configuration of a diol epoxide and the position of the methyl group have major effects on its reactivity with DNA. The greatest reactivity is seen in an R,S,S,R enantiomer with the methyl group and epoxide ring in the same bay region, e.g., the highly tumorigenic and mutagenic 5-MeC-1R,2S-diol-3S,4R-epoxide. Comparison of the dGuo/dAdo adduct ratios of the various diol epoxides with their tumorigenic and mutagenic activities suggests that dGuo adducts are important in the expression of biological activity of methylchrysene diol epoxides.

Chemical Phenomena↗