Pankaj K. Gadhia

Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU).

We report here the intercalation of 5-fluorouracil (5-FU), an anticancer drug in interlayer gallery of Na(+) clay (Montmorillonite, MMT), with the assistance of biopolymer (chitosan, CS). The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the drug intercalation into the clay interlayer space in support of CS and stabilized in the longitudinal monolayer by electrostatic interaction. In vitro drug release showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated significant reduction in DNA damage when drug was intercalated with clay and formulated in composites. The results of in vitro cell viability assay in cancer cells pointed at decreased toxicity of drug when encapsulated in Na(+)-clay plates than the pristine drug. In vivo pharmacokinetics, biodistribution, hepatotoxicity markers, e.g., SGPT and SGOT, and liver/testicular histology in rats showed plasma/tissue drug levels were within therapeutic window as compared to pristine drug. Therefore, drug-clay hybrid and composites can be of considerable value in chemotherapy of cancer with reduced side effects.

Montmorillonite/poly-(ε-caprolactone) composites as versatile layered material: Reservoirs for anticancer drug and controlled release property

This work evaluates intercalation of tamoxifen (Tmx) in interlayer gallery of Na(+)-MMT (Montmorillonite, MMT) (Tmx-MMT), which is further compounded with poly-(ε-caprolactone) (PCL) (Tmx-MMT/PCL, MPs), for oral chemotherapy of breast cancer. The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the intercalation of Tmx into the MMT interlayer that stabilized in the longitudinal monolayer mode by electrostatic interaction. No significant change in structural and functional properties of Tmx was found in the MMT layers. In vitro study of drug release profiles showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated moderate reduction in DNA damage when pristine Tmx was intercalated with MMT and formulated in composites. The Tmx-MMT hybrid efficacy was also confirmed on HeLa and A549 cancer cells by in vitro cell viability assay. In vivo pharmacokinetics (PK) of formulated Tmx in rats was examined and the results showed that plasma Tmx levels were within therapeutic window as compared to pristine Tmx. Therefore, Tmx-MMT hybrid and microcomposite particles (MPs) can be of considerable value in chemotherapy of malignant neoplastic disease with reduced side effects. This study clearly indicated that MMT not only plays a role as a delivery matrix for drug, but also facilitates significant increase in the delivery proficiency.

A Preliminary Study to Assess Possible Chromosomal Damage Among Users of Digital Mobile Phones

In a preliminary study to examine possible lymphocyte chromosomal damage, we have tested two cytogenetic endpoints, namely, chromosomal aberrations (CA) and sister chromatid exchange frequencies (SCE), in 24 mobile phone users (12 nonsmoker–nonalcoholic subjects and 12 smoker–alcoholics), who used digital mobile phones for at least 2 years, employing Gaussian Minimum Shift Keying modulations with uplink frequencies at 935–960 MHz. and downlinks at 890–915 MHz. For comparison, the control study group included another 24 individuals, matched according to their age, sex, drinking and smoking habits, as well as similar health status, working habits, and professional careers; but did not use mobile phones. Blood samples of 12 mobile users (6 smoker–alcoholic and 6 nonsmoker–nonalcoholic) and 12 controls (identical to mobile users in every respect) were further treated with a known mutagen Mitomycin‐C (MMC) to find out comutagenic/synergistic effect. A complete blood picture for each individual was assessed with an automatic particle cell counter. There was a significant increase (P < 0.05) in dicentric chromosomes among mobile users who were smoker–alcoholic as compared to nonsmoker–nonalcoholic; the same held true for controls of both types. After MMC treatment, there was a significant increase in dicentrics (P < 0.05) and ring chromosomes (P < 0.001) in both smoker–alcoholic and nonsmoker–nonalcoholic mobile users when compared with the controls. Although SCEs showed a significant increase among mobile users, no change in cell cycle progression was noted. The hematological picture showed only minor variations between mobile users and controls.

A preliminary cytogenetic and hematological study of photocopying machine operators

The incidences of chromosomal aberrations(CAs) as well as sister chromatid exchange frequencies (SCEs) was evaluated from 12 photocopying machine operators working on an average 8-9 hours per day for more than five years. A complete blood picture of each individual was assessed with an automatic particle cell counter. Additionally, blood pressure was measured at the time of blood collection from all photocopying machine operators. For comparison, the control group included another 12 individuals matched according to age, sex, socioeconomic conditions as well as other personal habits. The observations of the present study are indicators of health hazard for, although small, there was a significant increase in the percentage of aberrant cells (P<0.05), total aberrations (P<0.01) as well as total aberrations excluding chromatid gaps (P<0.01) among photocopying machine operators when compared to controls. However, results on SCE analysis of photocopying operators revealed no significant difference from the controls. At the same time all photocopying operators exhibited normal hematological parameters as well as blood pressure values.

Cytogenetic Analysis of Radiotherapeutic and Diagnostic Workers Occupationally Exposed to Radiations

Abstract The study group comprised of 12 occupationally exposed “radiotherapeutic and diagnostic workers”, working since last 12 years on an average (service duration 3 to 20 years), with 12 age and sex-matched controls not exposed to any kind of radiation and belonging to same socio-economic status as the radiation workers. Cytogenetic end points studied were CAs (Chromosomal aberrations), SCE (Sister chromatid exchange) and MN (Micronuclei). Hematological parameters were also studied. In addition, co-mutagenic/synergistic in vitro effects of known mutagen Mitomycin-C (MMC) on lymphocytes of these workers were evaluated. Results revealed a significant increase in dicentric (P < 0.05) as well as MN (P< 0.01) among radiation exposed workers when compared to controls. By contrast, no change in SCE frequencies and hematological parameters were observed. After in vitro MMC treatment CA (mainly dicentric and ring) increased significantly in lymphocytes of radiation exposed workers. Based on these observations, a preliminary indication of the study could be that long term low level radiation exposure may probably damage the genetic constitution of an individual.

Some Observations on Spontaneous Sister Chromatid Exchange Frequencies and Cell Cycle Progression in Stimulated Lymphocytes of Patients With Different Malignancies

Abstract Total 23 patients with different malignancies viz. Ca. Lung (5), Ca. Uterine & Cervix (5), Ca. Head & Neck (5), Sarcomas (5) and Malignant Melanoma (3); were studied for spontaneous sister chromatid exchange frequencies (SCE) as well as cell cycle progression. All blood samples were collected prior to chemotherapy and/or radiotherapy to exclude the influence of these therapies, if any, on SCEs. Totally 15 healthy, age and sex matched individuals and belonging to the same socio-economic status, but no direct relatives of the patients were studied simultaneously as controls. The SCE rates, when compared to controls (4.00 ± 0.39) were found to be significantly high for patients with Ca. lung (9.42 ± 1.20), malignant melanoma (8.14 ± 0.21), Ca. head & neck (6.85 ± 0.89) as well as sarcomas (6.29 ± 0.79). However, no detectable difference was observed in the SCE rate for patients with Ca. uterine & cervix (5.02 ± 0.88). Cell cycle proliferation and thereby replicative index was significantly elevated in patients with carcinoma of head & neck as well as malignant melanoma. On the other hand, rest of the patients showed no much variation in cell cycle progression when compared to controls.

Cytogenetic Study of Turner Syndrome and Its Variants

Abstract The principle objective of the present study was to investigate postnatal variants of Turner syndrome by cytogenetic study. Total of 1530 cases were referred to the researchers laboratory for cytogenetic analysis (karyotyping), out of which 61 cases of Turner syndrome (TS) diagnosed between March 2005 and January 2014. The most observed karyotype was classic 45,X (49.2 %) followed by iso(X) and iso(X) mosaic each (9.8 %) and least case of number one (1.6 %) was recorded with ring (Xr). Interestingly two cases of Robertsonian translocation t(13;14) were noticed which are considered to be rare. On the basis of clinical features of TS, such as primary or secondary amenorrhea with short stature, the confirmation was done by chromosomal analysis, karyotyping and FISH.

Cytome Assay of Buccal Epithelium for Bio-monitoring Genotoxic Assessment of Benzene Exposure among Petrol Pump Attendants

Abstract Petrol pump attendants are occupationally exposed to benzene through their contact with petrol vapor and engine exhaust. This study investigated the genotoxic effect associated with benzene exposure. Exfoliated buccal cells and urine samples were collected from 40 petrol pump attendants and 40 subjects as control group, their age and sex matched and they were not exposed to benzene. Further, these groups were classified into two subgroups: smokers and non-smokers. Cytogenetic study was carried out by cytome assay. To determine the benzene exposure, we have used metabolites of benzene such as phenol and trans, trans - muconic acid from urine. Frequencies of binucleated cells (P < 0.01), micronucleated cells (P < 0.01), bulging form nucleated cells (P < 0.01) and karyorrhectic cells (P < 0.01) were found to be significantly higher in petrol pump attendants than control individuals. Urinary mean phenol level (P < 0.01) and trans, trans - muconic acid levels (P < 0.01) were also found to be significantly high. Our study indicates that chronic and long term exposure of benzene can increase the genotoxic risk in petrol pump attendants.

Cytogenetic Studies on Railway Engine Drivers Exposed to Extremely Low Frequency Electromagnetic Fields (ELF-EMF)

Abstract Electric train engine drivers are occupationally exposed to relatively high magnetic field flux densities, while exposure to the other genotoxic agents is considered to be low or non-existent. The present study aimed to analyze the Chromosomal Aberrations (CAs) and Sister Chromatid Exchange (SCE) frequencies among the railway engine drivers occupationally exposed to ELF–EMF. Additionally, to know the synergestic/co–mutagenic effects, the blood samples of these individuals were exposed in vitroto 6ng/ml Mitomycin–C (MMC) and Chromosomal Aberrations (CAs) were studied. The results of the present study do not give any support to the hypothesis that occupational exposure to ELF–EMF can exert a genotoxic effect in these exposed individuals. In addition, it seems that ELF–EMF exposure along with Mitomycin–C (MMC) treatments does not influence the levels of Chromosomal Aberrations (CAs), indicating no possibility of synergestic/co–mutagenic effects.

Williams-Beuren Syndrome: A Rare Case from Western India

Williams-Beuren Syndrome (WBS) also known as Williams Syndrome (WS) is a rare multisystem genetic disorder having incidence of 1 in 20,000 to 50,000 live births. WS caused by deletion of 26 - 28 contiguous genes including elastin (ELN) on chromosome 7q11.23. It is characterized by congenital heart defects, skeletal and renal anomalies. We report herein two rare cases of WS (One male and one female) from Western India varying clinical presentation. The confirmation was carried out by cytogenetic analysis and FISH test.