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S Awasthi

Publications and source records attributed to S Awasthi.

At least 19 recordsLinked to original sources
PubMed1998

Gender-related differences in susceptibility of A/J mouse to benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis.

Benzo[a]pyrene (BP) is a suspected human carcinogen and is known to produce tumors in the lung and forestomach of mice. Glutathione (GSH) S-transferases (GST) play a major role in the detoxification of the ultimate carcinogen of BP, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE). Previous studies have shown gender-related differences in the expression of GST isoenzymes in mice. The present study was designed to test the hypothesis whether gender-related differences in the expression of GST isoenzymes can affect the susceptibility of mice to BP-induced lung and forestomach tumorigenesis. The expression of pi class isoenzyme mGSTP1-1, which is highly efficient in the detoxification of (+)-anti-BPDE, was approximately 3.0- and 1.5-fold higher in the liver and forestomach of male A/J mouse, respectively, as compared with the female. The levels of other major GST isoenzymes, mGSTA3-3 (alpha class), mGSTM1-1 (mu class) and mGSTA4-4 (alpha class), were also significantly higher in the liver of the male mouse as compared with the female. While pulmonary mGSTP1-1 expression did not differ significantly between male and female A/J mice, the expression of mGSTA3-3, mGSTM1-1 and mGSTA4-4 was significantly higher (1.4-4.0-fold) in the lung of the male A/J mouse as compared with the female. At lower concentrations of BP (0.5 mg BP/mouse), the tumor incidence/multiplicity was significantly higher in the lung as well as in the forestomach of female mice as compared with male mice. For example, while 30% of the female mice developed pulmonary tumors 26 weeks after the first 0.5 mg BP administration, none of the male mice had tumors in their lungs. At higher doses of BP (1.5 mg BP/mouse), however, this differential was either abolished or relatively less pronounced. Our results suggest that up to a certain threshold of BP exposure the levels of GST isoenzymes may be an important determinant of susceptibility to BP-induced tumorigenesis in mice.

Animals↗
PubMed1998

ATP-dependent transport of glutathione conjugate of 7beta, 8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene in murine hepatic canalicular plasma membrane vesicles.

Glutathione (GSH) S-transferases (GSTs) have an important role in the detoxification of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], which is the ultimate carcinogen of benzo[a]pyrene. However, the fate and/or biological activity of the GSH conjugate of (+)-anti-BPDE [(-)-anti-BPD-SG] is not known. We now report that (-)-anti-BPD-SG is a competitive inhibitor (Ki 19 microM) of Pi-class isoenzyme mGSTP1-1, which among murine hepatic GSTs is most efficient in the GSH conjugation of (+)-anti-BPDE. Thus the inhibition of mGSTP1-1 activity by (-)-anti-BPD-SG might interfere with the GST-catalysed GSH conjugation of (+)-anti-BPDE unless one or more mechanisms exist for the removal of the conjugate. The results of the present study indicate that (-)-anti-BPD-SG is transported across canalicular liver plasma membrane (cLPM) in an ATP-dependent manner. The ATP-dependent transport of (-)-anti-[3H]BPD-SG followed Michaelis-Menten kinetics (Km 46 microM). The ATP dependence of the (-)-anti-BPD-SG transport was confirmed by measuring the stimulation of ATP hydrolysis (ATPase activity) by the conjugate in the presence of cLPM protein, which also followed Michaelis-Menten kinetics. In contrast, a kinetic analysis of ATP-dependent uptake of the model conjugate S-[3H](2,4-dinitrophenyl)-glutathione ([3H]DNP-SG) revealed the presence of a high-affinity and a low-affinity transport system in mouse cLPM, with apparent Km values of 18 and 500 microM respectively. The ATP-dependent transport of (-)-anti-BPD-SG was inhibited competitively by DNP-SG (Ki 1.65 microM). Likewise, (-)-anti-BPD-SG was found to be a potent competitive inhibitor of the high-affinity component of DNP-SG transport (Ki 6.3 microM). Our results suggest that GST-catalysed conjugation of (+)-anti-BPDE with GSH, coupled with ATP-dependent transport of the resultant conjugate across cLPM, might be the ultimate detoxification pathway for this carcinogen.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

ATP-Dependent human erythrocyte glutathione-conjugate transporter. I. Purification, photoaffinity labeling, and kinetic characteristics of ATPase activity.

Dinitrophenyl S-glutathione (DNP-SG) ATPase is a 38 kDa membrane protein expressed in erythrocytes and other tissues. Although stimulation of ATP hydrolysis catalyzed by DNP-SG ATPase has been demonstrated in the presence of several structurally unrelated amphiphilic ions, structural and functional properties of this protein have not been well-defined. In the present study, we have developed an improved protocol for the purification of DNP-SG ATPase and investigated its kinetic and substrate-binding properties. The purification procedure was based on highly specific elution of the 38 kDa protein from DNP-SG affinity resin in the presence of ATP. The protein could not be eluted using either ADP or adenosine-5'-[beta,gamma-methylene]triphosphate (methylene-ATP), a nonhydrolyzable analogue of ATP. Doxorubicin (DOX), a weakly basic anthracycline chemotherapy agent, was found to be the preferred activator for stimulation of ATP hydrolysis by the enzyme. ATP binding to the enzyme was demonstrated using 8-azido-ATP photoaffinity labeling and binding of trinitrophenyl (TNP)-ATP, a fluorescent analogue of ATP. The photoaffinity labeling of DNP-SG ATPase (38 kDa) was saturable with respect to 8-azido ATP (Kd = 2 microM), indicating that the enzyme was capable of specific and saturable binding to ATP. DNP-SG binding was evident from the purification procedure itself and was also demonstrable by quenching of tryptophan fluorescence. Results of quenching of tryptophan fluorescence as well as radioactive isotope-binding studies indicated that DOX was bound to the purified protein as well.

Adenosine Triphosphatases↗
PubMed1998

ATP-Dependent human erythrocyte glutathione-conjugate transporter. II. Functional reconstitution of transport activity.

Purified dinitrophenyl S-glutathione (DNP-SG) ATPase was reconstituted into artificial liposomes prepared from soybean asolectin. Electron micrography confirmed the formation of unilamellar vesicles with an average radius of 0.25 micron. Intravesicular volume estimated by incorporation of radiolabled inulin into the vesicles was found to be 19.7 +/- 1.3 microL/mL reconstitution solution. Accumulation of the glutathione-conjugate of CDNB, DNP-SG, and of doxorubicin (DOX) in the proteoliposomes was increased in the presence of ATP as compared to equimolar ADP or adenosine 5'-[beta,gamma-methylene]triphosphate tetralithium. ATP-dependent transmembrane movement of DOX and DNP-SG into DNP-SG ATPase-reconstituted vesicles was saturable with respect to time, sensitive to the osmolarity of the assay medium, and temperature dependent. The energy of activation was found to be 12 and 15 kcal/mol for DNP-SG and DOX, respectively. Optimal temperature for transport was 37 degrees C. Saturable transport was demonstrated for DNP-SG (Vmax of 433 +/- 20 nmol/min/mg of protein, KmATP = 2.4 +/- 0. 3 mM and KmDNP-SG = 36 +/- 5 microM) as well as DOX (Vmax = 194 +/- 19 nmol/min/mg of protein, KmATP = 2.5 +/- 0.6 mM and KmDOX = 2.4 +/- 0.7 microM). The kinetic data for both DNP-SG and DOX transport were consistent with a random bi-bi sequential reaction mechanism. DOX was found to be a competitive inhibitor of DNP-SG transport with Kis of 1.2 +/- 0.2 microM and DNP-SG was found to be a competitive inhibitor of DOX transport with Kis of 13.3 +/- 2.6 microM.

Adenosine Triphosphatases↗
PubMed1998

Protein oxidation biomarkers in hyperoxic lung injury in rats: effects of U-74389.

Hyperoxia, used therapeutically in the treatment of respiratory insufficiencies, can cause lung injury, probably through the actions of reactive oxygen species. The present studies were designed to test the hypothesis that oxidation of specific proteins would provide useful biomarkers of the onset of tissue injury, and thereby provide clues as to the mechanisms responsible. We exposed adult male Sprague-Dawley rats to room air or to greater than 95% O2 for 60 h and examined proteins in pleural effusion and broncho-alveolar lavage (BAL) fluids, and in lung tissue homogenates and subfractions. Oxidation of protein thiols was assessed by derivatization with monobromobimane, separation by electrophoresis, and visualization of the fluorescent thioether derivatives. Derivatization with 2,4-dinitrophenylhydrazine (DNPH), electrophoresis, and western analysis was employed to assess a different class of oxidative modifications, frequently termed 'protein carbonyls'. In addition, we investigated the effects of the 21-aminosteroid U-74389G, 10 mg/kg, given intraperitoneally every 12 h, on biomarkers of protein oxidation and on manifestations of lung injury. Hyperoxia caused lung injury evidenced by pleural effusions, increases in BAL protein concentrations, and pulmonary edema; U-74389G attenuated the first two indices of lung injury, but did not alter edema. Protein thiol status of the fractions studied were not affected notably by hyperoxia, or by the aminosteroid. The formation of DNPH-reactive sites on a limited number of proteins by hyperoxia was observed, and some of these effects were attenuated in the animals given U-74389G. Histological examination of lung tissues showed accumulation of intra-alveolar protein exudates in hyperoxic rats, and a significant attenuation of this effect was observed in the animals treated with U-74389G. In conclusion, studies of shifts in protein thiol status that may be caused by hyperoxia will require increasingly specific methods of analysis, and characterization of the specific DNPH-reactive proteins formed in hyperoxia may provide critical insights into the mechanisms of lung injury. Administration of U-74389G offers some degree of protection against hyperoxia and attenuation of these biomarkers of oxidation, but the precise mechanisms by which this protection is effected will require additional study.

Animals↗
PubMed1998

Allylamine and beta-aminopropionitrile-induced vascular injury: enhanced expression of high-molecular-weight proteins.

In the present study we describe changes in aorta at the protein level associated with allylamine (AA) and beta-aminopropionitrile (beta APN) induced vascular toxicity in a rat model. This model represents a remarkable synergistic, necrotizing toxic effect of these combined toxins, and our rationale was to examine protein expression in order to shed light on the mechanisms underlying this synergism. Rats were given AA (100 mg/kg body weight/day) and beta APN (1 g/kg body weight/day) by gavage for 10 d; this protocol has been shown to result in smooth-muscle necrosis, but no visible connective tissue changes. Soluble and insoluble fractions from AA + beta APN- or from beta APN-treated aorta showed enhanced expression of three high-molecular-weight protein bands (ranges between approximately 120 and 95 kD). The time course of induction of proteins showed the appearance of AA + beta APN-induced specific proteins at d 3 of AA + beta APN treatment. Partial purification and characterization suggested that AA + beta APN specific proteins are likely to be collagen proteins (type I). Thus, the data presented in this article help in understanding the vascular toxicity induced by AA + beta APN or by beta APN, in that we have described an altered phenotypic expression of collagenous proteins indicative of selective medial vascular toxicity.

Administration, Oral↗
PubMed1998

Glutathione S-transferases of rabbit lung macrophages.

The catalytic activities of glutathione S-transferases (GSTs), particularly the alpha-class isozymes, can provide protection against oxidative stress through GSH-mediated metabolism of reactive products of lipid peroxidation. Lipid peroxidation products from oxidative metabolism in alveolar macrophages play an important role in mediating and regulating inflammatory response and injury in the lung. The rabbit has been used as an important animal model for studies of the role of alveolar macrophages in pulmonary pathology. Although rabbit lung macrophages display GST activity, the isozyme-specific expression of GSTs and the catalytic properties of these isozymes has not previously been defined. In present studies, we have purified the GST isozymes of rabbit alveolar macrophages obtained by bronchoalveolar lavage and performed immunologic and kinetic characterization of the purified isozymes. Results of our studies indicate the presence of three alpha-class isozymes (pI 10.2, 9.3, and 6.0) and one micro-class isozyme (pI 7.2). N-terminal sequence analysis of the micro-class isozyme indicated that it was distinct from the two previously described micro-class isozymes of rabbit. Kinetic studies indicated that two cationic alpha-class GSTs (pI 10.2 and 9.3) contribute the large majority of selenium independent GSH-peroxidase activity toward dilinoleoyl phosphatidylcholine hydroperoxide (kcat/Km values of 83.4 and 31.9 s-1 . M-1 . 10(3), respectively). A third alpha-class GST (pI 6.0) was shown to have highest catalytic activity toward conjugation of the 4-hydroxynonenal (4HNE) with GSH (kcat/Km = 1900 s-1 . M-1 . 10(3)). Structural and immunologic characterization of this GST isozyme indicated that it belongs to a subclass of the alpha-classGSTs selectively expressed in mesodermal origin cells that are exposed to high levels of oxidative stress and are characterized by high specific activity toward both lipid hydroperoxides and 4-HNE.

Aldehydes↗
PubMed1998

Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver.

Curcumin, an antioxidant isolated from turmeric (curcuma longa), has been shown to attenuate chemical carcinogenesis in rodents. Previous studies have shown that curcumin causes an increase in glutathione S-transferase (GST) activity in rodent liver which may contribute to its anti-cancer and anti-inflammatory activities. Since the effects of curcumin on specific GST isozymes and other glutathione (GSH)-linked enzymes are incompletely defined, we have examined in the present studies the effect of curcumin on hepatic non-protein sulfhydryls and GSH-linked enzymes in male Sprague-Dawley rats. When rats were fed curcumin at doses from 1 to 500 mg kg-1 body weight daily for 14 days, the induction of hepatic GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was found to be biphasic, with maximal induction of about 1.5 fold at the 25 to 50 mg kg-1 body weight dosage. At higher doses, a decrease was observed in the activity and in the rats treated with 500 mg kg-1 curcumin this activity was below the levels observed in controls. In contrast, GST activity towards 4-hydroxynonenal (4-HNE) increased in a saturable, dose dependent manner. Western-blot analyses of liver cytosols revealed that curcumin caused a dose dependent induction of rGST 8-8, an isozyme which is known to display the highest activity towards 4-HNE, a highly toxic product of lipid peroxidation. Glutathione peroxidase (GPx) activity towards cumene hydroperoxide in liver homogenate was also found to be increased in a saturable manner with respect to curcumin dose. Our results suggest that induction of enzymes involved in the detoxification of the electrophilic products of lipid peroxidation may contribute to the anti-inflammatory and anti-cancer activities of curcumin.

Animals↗
PubMed1997

Induction of glutathione S-transferase pi as a bioassay for the evaluation of potency of inhibitors of benzo(a)pyrene-induced cancer in a murine model.

There is a growing need for short-term and cost-effective bioassay to assess the efficacy of potential chemo-preventive agents. We report that the induction of glutathione (GSH) S-transferase pi (mGSTP1-1) by a chemo-preventive agent can be used as a reliable marker to assess its efficacy in retarding chemical carcinogenesis induced by benzo(a)pyrene (BP), which is a widespread environmental pollutant and believed to be a risk factor in human chemical carcinogenesis. This conclusion is based on 1) the relative contribution of mGSTP1-1 of the liver and forestomach of female A/J mice in the detoxification of the ultimate carcinogenic metabolite of BP, (+)-anti-7,8-dihydroxy-9, 10-oxy-7,8,9, 10-tetrahydrobenzo(a)pyrene [(+)-anti-BPDE]; and 2) a positive correlation between the induction of hepatic and forestomach mGSTP1-1 by 5 naturally occurring organosulfides (OSCs) from garlic (diallyl sulfide, diallyl disulfide, diallyl trisulfide, dipropyl sulfide and dipropyl disulfide) and their effectiveness in preventing BP-induced forestomach neoplasia in mice. In the liver, the combined contribution of other GSTs in the detoxification of (+)-anti-BPDE was far less than the contribution of mGSTP1-1 alone. Likewise, in the forestomach, the contribution of mGSTP1-1 far exceeded the combined contribution of other GSTs. Studies on the effects of OSCs against BP-induced forestomach neoplasia revealed a good correlation between their chemo-preventive efficacy and their ability to induce mGSTP1-1 expression in the liver (r = -0.89; p < 0.05) as well as in the forestomach (r = -0.97; p < 0.05). Our results suggest that the induction of mGSTP1-1 may be a reliable marker for evaluating the efficacy of potential inhibitors of BP-induced cancer in a murine model.

Allyl Compounds↗
PubMed1997

Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene.

The kinetics of the conjugation of glutathione (GSH) with anti-1, 2-dihydroxy-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-CDE), the activated form of the widespread environmental pollutant chrysene, catalyzed by two naturally occurring polymorphic forms of the pi class human GSH S-transferase (hGSTP1-1), has been investigated. The polymorphic forms of hGSTP1-1, which differ in their primary structure by a single amino acid in position 104, exhibited preference for the GSH conjugation of (+)-anti-CDE, which is a far more potent carcinogen than (-)-anti-CDE. When concentration of anti-CDE was varied (5-200 microM and the GSH concentration was kept constant at 2 mM, both hGSTP1-1(I104) and hGSTP1-1(V104) obeyed Michaelis-Menten kinetics. However, the Vmax of GSH conjugation of anti-CDE was approximately 5.3-fold higher for the V104 variant than for the I104 form. Calculation of catalytic efficiency (kcat/Km) thus resulted in a value for hGSTP1-1(V104), 28 mM-1 s-1, that was 7.0-fold higher than that for hGSTP1-1(I104), 4 mM-1 s-1. The mechanism of the differences in the kinetic properties of hGSTP1-1 isoforms toward anti-CDE was investigated by molecular modeling of the two proteins with GSH conjugation products in their active sites. These studies revealed that the enantioselectivity of hGSTP1-1 for (+)-anti-CDE and the differential catalytic efficiencies of the V104 and I104 forms of hGSTP1-1 in the GSH conjugation of (+)-anti-CDE were due to the differences in the active-site architecture of the two proteins. The results of the present study, for the first time, provide evidence for the toxicological relevance of GSTP1-1 polymorphism in humans and suggest that the population polymorphism of hGSTP1-1 variants with disparate enzyme activities may, at least in part, account for the differential susceptibility of individuals to environmental carcinogens such as anti-CDE and possibly other similar carcinogens.

Animals↗
PubMed1997

Active site architecture of polymorphic forms of human glutathione S-transferase P1-1 accounts for their enantioselectivity and disparate activity in the glutathione conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-ox y-7,8,9,10-tetrahydrobenzo(a)pyrene.

In this study, we demonstrate that the active site architecture of the human glutathione (GSH) S-transferase Pi (GSTP1-1) accounts for its enantioselectivity in the GSH conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10-tetrahydrobenzo(a) pyrene (anti-BPDE), the ultimate carcinogen of benzo(a)pyrene. Furthermore, we report that the two polymorphic forms of human GSTP1-1, differing in their primary structure by a single amino acid in position 104, have disparate activity toward (+)-anti-BPDE, which can also be rationalized in terms of their active site structures. When concentration of (+)-anti-BPDE, which among four BPDE isomers is the most potent carcinogen, was varied and GSH concentration was kept constant at 2 mM (saturating concentration), both forms of hGSTP1-1 [hGSTP1-1(V104) and hGSTP1-1(I104)] obeyed Michaelis-Menten kinetics. The V(max) of GSH conjugation of (+)-anti-BPDE was approximately 3.4-fold higher for hGSTP1-1(V104) than for hGSTP1-1(I104). Adherence to Michaelis-Menten kinetics was also observed for both isoforms when (-)-anti-BPDE, which is a weak carcinogen, was used as the variable substrate. However, (-)-anti-BPDE was a relatively poor substrate for both isoforms as compared with (+)-anti-BPDE. Moreover, there were no significant differences between hGSTP1-1(V104) and hGSTP1-1(I104) in either V(max) or K(m) for (-)-anti-BPDE. The mechanism of differences in kinetic properties and enantioselectivity of hGSTP1-1 variants toward anti-BPDE was investigated by modeling of the two proteins with conjugation product molecules in their active sites. Molecular modeling studies revealed that the differences in catalytic properties of hGSTP1-1 variants as well as the enantioselectivity of hGSTP1-1 in the GSH conjugation of anti-BPDE can be rationalized in terms of the architecture of their active sites. Our results suggest that the population polymorphism of hGSTP1-1 variants with disparate enzyme activities may, at least in part, account for the differential susceptibility of individuals to carcinogens such as anti-BPDE and possibly other similar carcinogens.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1997

Increased resistance to oxidative stress in transfected cultured cells overexpressing glutathione S-transferase mGSTA4-4.

Peroxidation of unsaturated fatty acids in membrane phospholipids is one of the multiple cytotoxic effects of oxidative stress. Lipid peroxidation is significant because a single initiating event triggers a chain reaction, thus amplifying the initial stimulus. Many oxidative stress-related pathologies have been linked to lipid peroxidation. Mouse glutathione S-transferase mGSTA4-4 exhibits high glutathione conjugating activity with toxic products of lipid peroxidation, e.g., 4-hydroxynon-2-enal. In addition, mGSTA4-4 has glutathione peroxidase activity toward phospholipid hydroperoxides. On the basis of these catalytic properties, we have previously proposed that the enzyme may be physiologically important in alleviating the cytotoxic effects of lipid peroxidation. We have now experimentally confirmed this hypothesis by transfecting HepG2 cells with mGSTA4 cDNA, and demonstrating a protective effect of expressed mGSTA4-4 protein on cells exposed during plating to H2O2, organic hydroperoxides, and phosphatidylcholine hydroperoxide. As compared to cells transfected with insert-free vector, a larger proportion of mGSTA4-transfected cells was able to attach to the culture dish, and continued to divide in the presence of the above compounds. In addition to alleviating the cytotoxic effects of oxidative stress, mGSTA4-4 may interfere with the subtoxic but cytostatic signals generated by a low-level pro-oxidant state.

Animals↗
PubMed1997

Rat GST 8-8 is expressed predominantly in myeloid origin cells infiltrating the gravid uterus.

Previous studies from our laboratory have shown a relatively high expression of rGST8-8 in uterine tissues. This GST isozyme displays relatively high glutathione-peroxidase activity towards lipid-hydroperoxides and towards toxic 4-hydroxyalkenals generated from lipid peroxidation. Since the uterus is a unique organ, subject to oxidative stress due to infiltration by immune effector cells during gestation and because this infiltration is readily identifiable histologically, the studies reported herein were performed to localize the cell specific expression of rGST8-8 to determine whether immune effector cells infiltrating the pregnant rat uterus specifically expressed rGST8-8. A 75 bp end-radiolabeled cRNA probe was prepared from the full length mGSTA4-4 cDNA from the region which is highly homologous with rGST8-8. This cRNA probe was used for in situ hybridization studies to localize rGST8-8 in specific cell types of gravid rat uterus. Results of these studies indicate that this GST isozyme is selectively expressed in myeloid origin cells such as monocytes/macrophages, and neutrophils infiltrating the uterine endometrium and in vascular walls. Selective expression of rGST8-8 in the myeloid origin cells, which are known to generate higher levels of reactive oxygen species, suggests that this GST isozyme plays an important role in the protection mechanisms against lipid peroxidation.

Animals↗
PubMed1997

Differential carcinogenicity of benzo[a]pyrene in male and female CD-1 mouse lung.

Benzo[a]pyrene (BaP) is known to induce tumors in lung, forestomach, and skin in experimental animals. Earlier studies have suggested that glutathione S-transferase pi (GST pi) is involved in the detoxification of the "ultimate" carcinogenic metabolite of BaP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). The constitutive expression of GST pi in the liver of the male CD-1 mouse is higher than that of the female, and BHA has been shown to preferentially induce GST pi in the female as compared with the male mouse. The present studies were therefore designed to compare the susceptibility of male and female CD-1 mice to the carcinogenic effects of BaP and the protective effect of BHA. Results of these studies show that the female CD-1 mice are more susceptibile to the carcinogenic effect of BaP than the males and that the attenuation of BaP-induced carcinogenesis by BHA appears to be restricted only to the females.

Adenocarcinoma↗
PubMed1997

Prevalence of malnutrition and intestinal parasites in preschool slum children in Lucknow.

OBJECTIVE: To assess the point prevalence of intestinal parasites and their association with nutritional parameters. SETTING: Anganwadi centers under the Integrated Child Development Scheme (ICDS) in Lucknow, North India. DESIGN: Cross-sectional survey. METHODS: By random draw, 32 out of 153 Anganwadi centers were selected. All eligible subjects registered with the Anganwadi worker were enrolled. These were 1061 children (48.3% girls and 51.7% boys) between the ages of 1.5 to 3.5 years. RESULTS: Of these, 67.6% were underweight (weight for age < -2 SD), 62.8% were stunted (height for age < -2 SD) and 26.5% were wasted (weight for height < -2 SD). Parasites were detected in 17.5% (95% CI 15.3%-19.9%) children by a single direct fecal smear examination. Of these, Ascaris lumbricoides was found in 124 (68.1%) and Giardia lamblia in 60 (32.9%). There was no association between weight or height and parasite positivity. The mean hemoglobin levels for children who were smear positive versus smear negative for ascaris or giardia were 9.1 g/dl and 9.6 g/dl, respectively (p < 0.0001). CONCLUSION: In the urban slums the point prevalence of intestinal parasites is 17.5% in the preschool children. Malnutrition and low hemoglobin levels are also widely prevalent. Urgent remedial steps are needed on community basis to improve their nutritional status and control parasitic infestation.

Animals↗
PubMed1997

Cardiovascular responses to treadmill exercise testing in anemia.

OBJECTIVE: To study exercise performance on a treadmill in anemic children. DESIGN: Prospective case control study. SETTING: Department of Pediatrics and Intensive Care Unit, Department of Medicine, King George's Medical College, Lucknow. SUBJECTS: The study population consisted of 41 cases of anemia (10 mild, 21 moderate and 10 severe) and 11 normal age and height matched children aged between 7-12 years. METHODS: These subjects were exercise tested on Quinton Model Q5000 treadmill using Modified Naughton Q5000 protocol. Heart rate, systolic blood pressure, double product, ECG changes, exercise duration and metabolic equivalents achieved during peak exercise were studied. Statistical analysis was performed using analysis of variance (ANOVA) test. RESULTS: No significant difference was observed in values of resting heart rate, heart rate at peak exercise, recovery heart rate, blood pressure response, resting double product, double product at peak exercise, recovery double product and ECG changes in any of the study groups (p > 0.05). However, the gain in heart rate at peak exercise compared to basal value, and double product, total exercise duration and metabolic equivalent (MET) values at peak exercise were significantly low in anemic children on comparison to normal controls (p < 0.001). CONCLUSIONS: Cardiovascular responses are blunted in anemia, mainly because of depleted cardiac reserve.

Analysis of Variance↗
PubMed1997

Seasonal pattern of morbidities in preschool slum children in Lucknow, north India.

OBJECTIVE: To quantify the burden of common morbidities for each month in one year, in preschool children. SETTING: Anganwadi centers under the Integrated Child Development Services Scheme (ICDS) in Lucknow, North India. DESIGN: Prospective cohort study, METHODS: From 153 anganwadi centers in urban Lucknow, 32 were selected by random draw. All eligible children registered with the anganwadi worker were enrolled over a period of six months from July 1995 to January 1996. All the subjects were then contacted a second time six months later. SUBJECTS: There were 1061 children (48.3% girls and 51.7% boys) between the ages of 1.5 to 3.5 years. RESULTS: The annual incidence rate (IR) per 100 child-years for respiratory, diarrhea and skin diseases and pneumonia were 167, 79.9, 30.6 and 9.6, respectively. When compared to other seasons, the IR of pneumonia was lowest in the winter months (October to February) while those of diarrhea and skin diseases were the highest in summer (March-June) and monsoon (July to September) months, respectively. Season specific diseases were measles in summer, and fever as the isolated symptom in monsoon. The IR for combined morbidities was the highest in the monsoon as compared to winter months. CONCLUSIONS: Season specific intensification of existing health care resources for these morbidities can be considered. Similar studies are needed from other parts of the country.

Child, Preschool↗