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Biomedical subjects

S G Adhvaryu

Publications and source records attributed to S G Adhvaryu.

At least 19 recordsLinked to original sources

Familial supernumerary marker chromosome evolution through three generations.

A mosaic chromosome complement, 46,XY/47,XY,+r(15), was detected at prenatal diagnosis. Family studies showed the mother and one of her two children to have a bisatellited supernumerary marker chromosome (SMC) in all lymphocytes examined. The maternal grandfather also showed a bisatellited SMC, but in only 2 per cent of his lymphocytes. NOR, DA/DAPI, and chromosome 15 centromere and short arm-specific probes confirmed the identify of the bisatellited SMC and of ring SMC as derived from chromosome 15. An apparently normal male was born at full term. At age 1 year, the baby continues to have normal growth and development. The bisatellited 15 likely originated by somatic mutation in the grandfather (2 per cent cells), was transmitted unchanged to the daughter and grandson (germline transmission, no mosaicism), and then evolved by excising the satellites and forming a ring SMC in the index case. Progressive changes in the frequency and subsequent changes in the structure of this SMC illustrate the unusual characteristics of chromosome 15.

Adult↗

Urine of tobacco/areca nut chewers causes genomic damage in Chinese hamster ovary cells.

The chromosome-damaging effects of urine concentrates (UCs) from tobacco plus areca nut (T/AN) chewers (a highly popular habit and a major risk factor for oral cancer in India) were evaluated on Chinese hamster ovary (CHO) cells employing two cytogenetic end-points, namely chromosome aberration (CA) and sister chromatid exchange (SCE) frequencies. Urine creatinine levels were comparable between controls and T/AN chewers. CA and SCE frequencies in CHO cells were found to be elevated significantly (P < 0.001) following treatment with UCs prepared from T/AN chewers (UC-T/AN chewers) as well as with UCs of non-chewer controls (UC-control subjects). Moreover, elevation of these two parameters by UC-T/AN chewers was significantly higher in comparison to that of UC-controls. The results of the present study indicated that besides the oral cavity, which is a target organ for T/AN chewers, mutagens/carcinogens in tobacco and areca nut might be playing a causative role in cancer of the urinary bladder as well.

Animals↗

Pan masala--a genotoxic menace.

Cytogenetic markers such as chromosome aberration (CA), sister-chromatid exchange (SCE) and micronucleated cells (MNC) were used to assess the genotoxic potential of dimethyl sulphoxide (DMSO) extract of pan masala with and without tobacco (PM-T and PM). Using in vitro short-term assays, the extracts were tested in the presence or absence of metabolic activation. In cultures without metabolic activation the extracts were found to increase the frequency of all the three parameters tested significantly, however those with activation elicited a weak response, implying that pan masalas contain solvent (DMSO)-soluble direct-acting mutagen.

Animals↗

Ethanol potentiates the clastogenicity of pan masala--an in vitro experience.

The significance of the interaction between alcohol and tobacco in causing head and neck cancers is well documented. Our previous reports on in vitro studies using aqueous and organic extracts as well as cytogenetic studies among pan masala consumers have conclusively shown the genotoxic potential of pan masala--a dry mixture of the areca nut, lime, catechu, unspecified flavouring agents, etc., often containing tobacco in it and is widely consumed in India. Now in the present report, the clastogenic effect of ethanol and pan masala in different combinations was evaluated on Chinese hamster ovary cells utilizing chromosome aberration (CA) frequency as an endpoint. An ethanol concentration of up to 2.0% had no effect on CA/cell value. The low-dose continuous treatment and high-dose short-term pre-, post- and simultaneous treatment of ethanol and aqueous extract of pan masala with and without tobacco yielded dose-dependent elevations in CA frequency, compared to any of these two substances alone. Thus, these results provide evidence that alcohol consumption may potentially increase the risk of oral cancer among pan masala chewers.

Animals↗

Evaluation of chemopreventive effects of betel leaf on the genotoxicity of pan masala.

The antigenotoxic effect of the aqueous extract of betel leaf (BL-ext.) against the pan masala was tested with the help of cytogenetic endpoints like chromosome aberration (CA) and sister chromatid exchange (SCE) utilizing Chinese hamster ovary (CHO) cells. Compared to the cultures treated with aqueous extract of pan masala alone, a reduction in CA and SCE frequencies in CHO cells was observed following a combined treatment with pan masala (with or without tobacco) extract and BL-ext. The protective effect of BL-ext. against the genomic damage caused by pan masala was statistically significant only after treating the cells for a longer period.

Animals↗

Serum lactate dehydrogenase and its isoenzymes in leukemia patients: possible role in diagnosis and treatment monitoring.

Serum levels of total LDH (T.LDH) and LDH isoenzymes in 145 untreated leukemia patients were examined and compared with those of 150 age and sex matched healthy individuals (controls) and 77 anemia patients (pathological controls). As compared to the controls, T.LDH, LDH-1, LDH-2, LDH-3, LDH-4 and LDH-5 values were significantly elevated (p < 0.001) in untreated leukemia patients. T.LDH, LDH-1, LDH-2 and LDH-3 levels were significantly raised in anemia patients as compared to the controls. A significant increase in the levels of T.LDH, LDH-2, LDH-3 and LDH-4 was observed in untreated leukemia patients as compared to the anemia patients. LDH-4 was most specific (81.0%), while LDH-2 was the most sensitive (84.0%) marker for leukemia. Mean values of all the markers were higher in leukemia patients with persistent leukemic activity/accelerated leukemic phase as compared to the patients in remission. Serum levels of T.LDH as well as all the five isoenzymes were significantly lower in leukemia patients in remission as compared to untreated leukemia patients. The study indicated that alterations in T.LDH and its isoenzymes are useful for diagnosis and treatment monitoring of leukemia.

Anemia↗

Clinical significance of serum total and heat-stable alkaline phosphatase in leukemia patients.

AIMS AND BACKGROUND: Variations in serum alkaline phosphatase (ALP) and placental-like (heat stable) alkaline phosphatase (PLAP) are found to be clinically useful in cancer patients. The present study evaluated serum ALP and PLAP levels to establish a blood-based biochemical index for leukemia patients. STUDY DESIGN: ALP and PLAP levels were determined in 145 untreated leukemia patients, 77 anemia patients, 150 healthy individuals (controls), 47 leukemic patients in remission and 23 patients with persistent leukemic activity/accelerated leukemic phase (P. Leu./A. Leu.). The enzymes were estimated with highly specific spectrophotometric methods. RESULTS: Serum ALP and PLAP levels were significantly elevated in anemia patients and leukemia patients compared to controls. Comparison between anemia patients and leukemia patients showed insignificant differences for ALP, whereas PLAP levels were significantly raised (p < 0.001) in leukemia patients. ALP showed insignificant difference between untreated leukemia patients, patients with P. Leu./A. Leu. and leukemia patients in remission. PLAP levels were comparable in patients with P. Leu./A. Leu. and were significantly lower (p < 0.02) in leukemia patients in remission than in untreated leukemia patients. CONCLUSIONS: The results indicate that serum PLAP levels are a useful biochemical marker for diagnosis and treatment monitoring of leukemia patients. However, serum ALP levels have limited utility for leukemia patients.

Adolescent↗

Genotoxic effects of tobacco extract on Chinese hamster ovary cells.

Genotoxic effects of an aqueous extract of Nicotiana tabacum, a variety commonly used in India for chewing purposes, were analysed on CHO cells utilizing two different cytogenetic end-points, namely, chromosome aberration frequency and sister chromatid exchange frequency. Statistically significant elevations in the values of both the markers clearly indicated chromosome damaging effects of the extract. Elevations in chromosome aberration and sister chromatid exchange frequencies are suggestive of intrastrand and interstrand DNA cross-links following exposure to tobacco. The effects observed following treatment with low dose for longer duration are of relevance to the condition of the oral mucosa of the chronic smokeless tobacco users.

Animals↗

Incidence of micronuclei in oral mucosa of users of tobacco products singly or in various combinations.

Frequencies of micronucleated cells (MNCs) were analyzed in the exfoliated buccal mucosa of normal healthy individuals from different parts of India who were regularly using either areca nut alone, mava, tamol, tobacco with lime, dry snuff or masheri. The analyses were also carried out among oral submucous fibrosis patients who had the habit of chewing either mava or areca nut. Compared with 'no habit' healthy individuals, all the groups, irrespective of their type of habit, had significantly higher frequencies of MNCs.

Adolescent↗

Role of areca nut consumption in the cause of oral cancers. A cytogenetic assessment.

BACKGROUND: Cytogenetic studies, framed to assess the possible genomic damage caused by areca nut consumption (without tobacco and not as a component of betel quid), were performed among areca nut chewers, which included normal people who chew areca nuts, patients with oral submucous fibrosis, and patients with oral cancer, and healthy nonchewing controls. RESULTS: The analysis showed statistically significant increases in the frequencies of sister chromatid exchanges and chromosome aberrations in peripheral blood lymphocytes and the percentage of micronucleated cells in exfoliated cells of buccal mucosa among all three groups of chewers when compared with those of the controls. CONCLUSIONS: The current data, the first of this type among only areca nut chewers, highlight that this popular masticatory is erroneously considered "safe" and that it increases the genomic damage even when chewed without tobacco. The data also signify that, henceforth, in cytogenetic biomonitoring, areca nut consumption also should be considered as one of the confounding factors.

Areca↗

Chromosome damaging effects of pan masala.

Effects of aqueous extracts of a popular brand of pan masala with and without tobacco (PM-T and PM) were studied for short duration treatment employing an in vitro system. Metabolic activation with S9 mix was also included. Frequency of all the three cytogenetic endpoints viz., chromosome aberration (CA); sister chromatid exchange (SCE) and % micronucleated cells (% MNC) were found to be elevated significantly in a dose-dependent manner in cultures without metabolic activation. However, addition of S9 activation system resulted in suppression of chromosomal damage. Our findings indicate that pan masalas contain water soluble direct acting mutagens.

Animals↗

In vitro genotoxic effects of areca nut extract and arecoline.

The genotoxic potential of the aqueous extract of areca nut as well as arecoline, the major alkaloid of the areca nut, was tested with the help of cytogenetic markers such as sister-chromatid exchanges and chromosome aberrations, utilizing Chinese hamster ovary (CHO) cells. The continuous-treatment and pulse-treatment schedules yielded dose-dependent elevations in the frequencies of sister-chromatid exchange and chromosomal aberration in CHO cells, indicating a genotoxic effect of both the extract and arecoline. The results also imply that, besides arecoline, there may be some other water-extractable substances in the areca nut that make the extract more genotoxic. The chromosome damage was found to be more severe on treating the cells with low concentrations and for longer duration, which mimic the effects of chronic areca nut consumption.

Animals↗

Variations in centromeric heterochromatin among patients with pre-malignant and malignant oral diseases.

Polymorphism of heterochromatic regions of chromosomes 1, 9 and 16 was studied in 60 oral cancer patients, in 40 patients with oral submucous fibrosis (OSMF) and in 60 normal healthy subjects. The size heteromorphism was significantly greater (p less than 0.001) in chromosome I of the patients. Localization variants were also significantly more frequent among the patients (p less than 0.05 for OSMF and less than 0.001 for oral cancer patients). The C-band heteromorphism patterns remained comparable in OSMF and in oral cancer patients, with chromosome I being the most frequently involved. On correlating the tobacco/areca-nut chewing habit with the presence of C-band heteromorphism, we observed that C-band heteromorphism was present in 89% of the habit-free oral cancer patients and 80% of the OSMF patients with relatively shorter exposure to this habit, i.e. less than 5 years. This signifies that genetic factors are important in the causation of oral precancerous and cancerous conditions and that polymorphism of the heterochromatic regions does appear to play a role in these conditions.

Adult↗

Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity.

Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease.

Biomarkers↗

Cytogenetic surveillance of tobacco-areca nut (mava) chewers, including patients with oral cancers and premalignant conditions.

Three cytogenetic endpoints were studied in non-chewing healthy controls and 3 groups of tobacco-areca nut chewers, viz. normal chewers, chewers with oral submucous fibrosis and chewers with oral cancer. Frequencies of sister-chromatid exchanges and chromosome aberrations in peripheral blood lymphocytes and of micronucleated cells in exfoliated buccal mucosa were evaluated. All the parameters showed statistically significant elevations in all 3 groups of chewers compared to the controls. The data indicate possible application of the parameters as sensitive endpoints for monitoring tobacco-areca nut chewers, the group of individuals at higher risk of developing oral cancer, the commonest cancer among Indian males.

Adolescent↗

Cytogenetic studies reveal increased genomic damage among 'pan masala' consumers.

Pan masala (PM), a dried powdered mixture containing ingredients like areca nut, catechu, lime, cardamom and flavouring agents, is consumed abundantly by Indians and is also exported to Western countries. Pan masala with tobacco (PM-T) is also available on the market. In view of the role of the ingredients of PM in the causation of oral diseases, the possible harmful effects of consuming this complex mixture were analysed in individuals regularly consuming PM and among healthy non-consuming controls without any habit. Three cytogenetic endpoints and two tissues were employed to assess possible DNA damage. Sister chromatid exchange and chromosome aberrations were estimated in the peripheral blood lymphocytes, tissues indirectly exposed to the substance and the frequency of micronucleated cells was scored in the tissue directly in contact with PM, i.e. the exfoliated buccal mucosa cells. All three cytogenetic endpoints demonstrated a statistically significant increase (P less than 0.001) among the PM consumers as compared with the non-consuming controls.

Adult↗

C-band heterochromatin variants in individuals with neoplastic disorders: carcinoma of breast and ovary.

C-band heteromorphism was studied in 106 females, including 71 patients with breast cancer or ovarian cancer. Size heteromorphism and localization variants (inversions) were scored separately. Compared to 22.86% of controls, 70.42% of the cancer patients were heteromorphic for the size of C-band. The localization variants were observed in only 8.57% controls, whereas 42.25% of cancer patients carried such variants. Taking both the criteria together, compared to 31.43% controls, 80.28% cancer patients were C-band heteromorphic. The present study supports the reported association between presence of C-band heteromorphism and occurrence of a malignant disease.

Breast Neoplasms↗

Assessment of genotoxicity of nicotine employing in vitro mammalian test system.

Genotoxicity of nicotine was evaluated employing Chinese hamster ovary (CHO) cells. Two cytogenetic endpoints, viz. frequency of sister chromatid exchange (SCE) and chromosome aberration (CA) were considered. Nicotine was found to induce CA and SCE frequency in a dose and duration dependent manner. Statistically significant elevations in CA frequency were observed only with higher concentrations of nicotine, whereas, SCE frequencies were increased significantly by all the doses utilized. It was genotoxic at the concentration, comparable to the saliva levels of nicotine achieved during tobacco chewing. The results obtained by continuous and pulse treatments with nicotine explain the harmful effects of chronic tobacco consumption.

Animals↗