Irradiated Parental Cells Research Articles

Ionising radiation and trans-generational instability

Ionising radiation and trans-generational instabilityBackground. Indirect monitoring of the impact posed by ionising radiation to the genome instability of the descendants, consequent to the irradiation of one of their parents, boils down to the investigation of changes occurring exclusively in the mini-satellite loci of the cells constituting the gametal developmental line. The resultant mini-satellite mutations are expressed in their percentages, and equal to the ratio of the number of mutated alleles in that particular generation over the total number of alleles present. The impact of ionising radiation to the irradiated parent's offspring was first noticed on haematopoietic mouse stem-cells. Even though an irradiated cell of a female parent lacks any mutations whatsoever, daughter cells present with the increased mutation rates. The observed phenomenon of the so called trans-generational instability has been defined as the occurrence of mutations in the genome of individuals originating from the irradiated ancestors. Due to the aforementioned, one can conclude that these mutations need not be present in the irradiated parental cells, and do not necessarily vanish in the next few generations, but may result in the increase in mutation rates observed in the latter.Conclusions. The results of the investigations performed on the animal model, as

Augmentation of local antitumor immunity in the liver by tumor vaccine modified to secrete murine interleukin 12.

Minimal residual lesions have been a major problem in surgical management of cancer. We transfected M5076 with murine IL-12 gene by a retroviral vector, established a stable transfectant secreting IL-12 and investigated its antitumor effects on a spontaneous liver metastasis murine model of M5076 reticulum cell sarcoma. Subcutaneous vaccination of the irradiated transfectant into the remote skin following the amputation of the tumor-bearing limb improved survival when compared with the vaccination of irradiated parental cells (control). Cytotoxic activities against parental M5076 were significantly stronger in the hepatic lymphocytes from the mice vaccinated with the IL-12 transfectant than those from the control. IFN-gamma production of hepatic lymphocytes when they were cocultured with the parental cells was significantly augmented in mice vaccinated with the IL-12 transfectant compared with the control. On the other hand, both cytotoxic activity and IFN-gamma production of spleen cells in the M5076-vaccinated and transfectant-vaccinated mice were at similar levels. Immunophenotypic analysis revealed the selective increase of CD3+NK1+ population in the liver from the transfectant-vaccinated mice. These results suggest that tumor vaccines genetically modified to secrete IL-12 continuously at a relatively low level preferentially augment local antitumor activity in the liver rather than systemic immune responses. This strategy warrants further investigation as an adjuvant modality in the management of postoperative residual tumors.

Immunization against a rat colon carcinoma by sodium butyrate-treated cells but not by interleukin 2-secreting cells

Background & Aims Vaccination of patients with colon cancer with irradiated autologous tumor cells and bacille Calmette-Guérin (BCG) was reported to augment mean survival. It was recently observed that a local treatment combining recombinant interleukin 2 and the differentiation agent sodium butyrate cured rats with colon cancer peritoneal carcinomatosis. To optimize vaccination protocols, the comparison of the efficacy of irradiated tumor cells mixed with BCG with that of interleukin 2-gene-transfected cells and of tumor cells pretreated with sodium butyrate was performed. Methods The poorly immunogenic rat colon carcinoma cells PROb were used in a vaccination assay. Interleukin 2-transfected PROb ceils, either proliferating or irradiated, were used. The efficiency of irradiated PROb cells mixed with BCG, of interleukin 2-transfected cells, or of cells pretreated with sodium butyrate was tested. Results Vaccination with irradiated parental cells and BCG did not provide protection. Irradiated interleukin 2-transfected cells were poorly efficient in the vaccination assay. Conversely, vaccination with irradiated parental cells pretreated with sodium butyrate before injection provided good protection. Conclusions Interleukin 2-secreting cells efficiently vaccinated animals when injected while replicating but not after irradiation. Conversely, sodium butyrate pretreatment provided a simple and efficient vaccination scheme that generated a long-term immune memory and allowed the use of irradiated cells.