We have recently reported that DNA and chromatin fragments derived from apoptotic cells that circulate in blood of human beings can readily enter into somatic cells of mice in vitro and in vivo, evoke a DNA damage repair response and integrate themselves into their genomes. However, these findings are at odds with established knowledge on two counts: first, DNA is not known to spontaneously enter into cells, and second, DNA is not known to have any intrinsic biological properties.

Following cue from the above in vitro experiments, we undertook in vivo studies of R-Cu to test its Cfs-degrading activity.

Since our study shows that Cfs are DNA damaging agents with implications for diseases associated with elevated Cfs levels, removal / degradation of Cfs could be of therapeutic value. Resveratrol (R), a plant polyphenol, is known to reduce Cu (II) to Cu (I) generating reactive oxygen species that can cleave plasmid DNA.

Radiation induced by-stander effect (RIBE) is a poorly understood phenomenon wherein non-irradiated cells show evidence of DNA damage, genomic instability, mutation and apoptosis bothin vitro and in vivo. We have observed that chromatin fragments (Cfs) that are released from dead cells resulting from radiation treatment are one of the key factors responsible for RIBE.

Since our study shows that Cfs are DNA damaging agents with implications for diverse diseases associated with elevated Cfs levels, removal of Cfs could be of therapeutic value. We have developed pullulan-based histone antibody nanoconjugates for the removal of Cfs from circulation. Nanoconjugates were developed and various physico-chemical characterizations were carried out. The efficacy of these nanoconjugates on removing Cfs was evaluated both in vitro and in vivo.

There is a long held belief among medical doctors and scientists that metastatic tumours are histologically similar to the primary. This belief is reified because it supports the prevailing theory of cancer metastasis. The latter teaches that tumour cells detach from the primary site to intravasate into the blood stream reach distant organs where they extravasate into the target tissues and grow  to form a metastatic cancer.

Following our observation that circulating Cfs are DNA damaging and oncogenic agents, we investigated whether application of dead cancerous cells (dcCfs) to NIH3T3 cells will bring about similar pathological changes. We found that numerous dcCfs exiting from the dead cells rapidly entered into the recipients, integrated into their genomes and triggered genome-wide de-regulation of transcription. Whole genome sequencing of NIH3T3 cells treated with dead human cancer cells detected several hundred thousand human reads in recipient mouse cells.