Background: Tobacco chewing is attributed to oral cancer. Prediction of cancer development by genotoxicity analysis is a major challenge to identify tobacco users at greater risk. Therefore, present study aimed to analyze tobacco related genotoxic effects in chewers monitoring micronuclei (MN) and chromosome aberrations (CA). The biomarkers were compared with non chewer to (i) predict risk for genotoxicity, (ii) estimate synergistic effect of tobacco exposure with level of biomarkers, and (iii) identify best cellular site of measurements for genotoxicity assessment. Methods: Healthy tobacco chewers (n=47); and controls (n=48) were enrolled in the study. The peripheral blood lymphocyte and exfoliated buccal mucosa cells were studied for CA and micro nucleated cell count (MNC) respectively. An arbitrary unit was obtained for Lifetime Tobacco Exposure (LTE) using frequency/day multiplied by duration of years of tobacco use. Data were analyzed using SPSS statistical software. Results: MNC was significantly higher (p=0.001) in chewers than controls. CA was higher in chewers than controls. MNC can differentiate higher tobacco exposure in chewers than CA. Controls having MNC above cutoff level have greater risk of genotoxic exposition (95% C.I.; 1.462-23.26, p=0.012). Conclusion: The present study concludes that MNC is a better surrogate biomarker to predict genotoxicity than CA for tobacco exposure and DNA damage index in tobacco chewers

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The BCR/ABL gene rearrangement is cytogenetically visualized in most chronic myeloid leukemia (CML) cases. About 5-10 % of CML patients lack its cytogenetic evidence, however, shows BCR/ABL fusion by molecular methods. We describe two CML patients with Philadelphia (Ph) negative (-ve) and BCR/ABL positive by fluorescence in situ hybridization (FISH). Both the cases were in chronic phase at diagnosis. Conventional cytogenetics and different FISH assays were adopted using BCR/ABL probes. Home-brew FISH assay using bacterial artificial clone (BAC) for BAC-CTA/bk 299D3 for chromosomal region 22q13.31-q13.32 was performed in case 1. Both the patients were Ph-ve. In first case, dual color dual fusion (DCDF)-FISH studies revealed 1 Red (R) 2 Green (G) 1 Fusion (F) signal pattern in 80 % of cells indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph and 2G2F signal pattern in 20 % of cells indicating two BCR/ABL fusions on both chromosomes 9q34 on presentation. In second case, FISH studies revealed the 1R1G1F signal pattern indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph in 100 % of cells at presentation. During follow-up, both the patients exhibited 2G2F signal pattern indicating two BCR/ABL fusions on both chromosomes 9q34, which indicated a clonal evolution in 100 % cells. Both the patients did not achieve therapeutic response. Relocation of BCR/ABL fusion sequence on sites other than 22q11 represents a rare type of variant Ph, the present study highlights the hot spots involved in CML pathogenesis and signifies their implications in Ph-ve BCR/ABL positive CML. This study demonstrated the genetic heterogeneity of this subgroup of CML and strongly emphasized the role of metaphase FISH, especially in Ph-ve CML cases, as it detects variations of the classical t(9;22).

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