Page 66 - 2014 Printable Abstract Book
P. 66
(S1503) The role of DNA repair in radiation induced carcinogenensis. Fen Xia, Ohio State University,
Columbus, OH
Radiation induced carcinogenesis is one of the detrimental side effects of radiation therapy. Ionizing
radiation directly or indirectly induces DNA damage and generates various toxic lesions. It has been
proposed that mutations resulted from misrepaired DNA lesions lead to gnomic instability and play
important role in tumor initiation and progression. However, the regulation of multiple pathways in repair
radiation induced DNA damage, the effect of repair processes on genomic instability, and the role of DNA
repair in radiation induced carcinogenesis still remains to be clarified. In this review, we will focus on
recent findings on how DNA double-strand break repair machineries are affected by exposure to ionizing
radiation and during proliferation, and will discuss how repair of double strand breaks may be a key player
in the process of radiation-induced carcinogenesis.
(S1504) Abscopal effect: much more than a conceptual dichotomy. Mariateresa Mancuso, ENEA, Rome,
Italy
In the last ten years, the concept that radiation generates long-range signaling responses has been
described in a wide variety of experimental systems (in vitro, cultured artificial 3-D human tissue systems,
ex vivo models), suggesting a need for a new paradigm in radiation biology. In this scenario, our own
research activities are focused on in vivo validation of non-targeted effects, with particular attention to
implications for cancer development. From a biologist’s point of view, abscopal effects induced by
radiation include induction of genomic instability, cell death, and oncogenic transformation in normal
tissues outside the irradiated volume. Using a mouse model of radiation sensitivity, we provided the first
proof-of-principle that non-targeted (abscopal) effects are factual in vivo events with carcinogenic
potential in different tissues (i.e., CNS and skin), suggesting a key role of gap junction intercellular
communication in transmission of oncogenic radiation signals to un-hit tissues. Moreover, we established
that interplay between radiation dose and exposed tissue volume plays a critical role in non-targeted
effects, including carcinogenesis, occurring in off-target tissues. Besides this detrimental significance,
abscopal effects may also lead to beneficial consequences. In fact, from the oncologist’s perspective, the
term refers to distant tumor regression after localized irradiation, and anti-tumor abscopal effects have
been clinically well documented. Recently, we have experimentally demonstrated that abscopal effects
induced by radiation are able to sterilize non-irradiated tumor cells depending on the presence of wt p53,
raising the intriguing hypothesis that the tumor biology could have a key role in development of
personalized radiotherapy protocols. Although radiation induced non-targeted effects have been studies
mostly in terms of cancer induction, there is recent evidence from my laboratory that it is also link to
development of non-cancer effects, mainly cardiovascular. Results supporting these conceptual
dichotomies of radiation abscopal effects will be presented and discussed. Supported in part by Grant
10357 from AIRC and “PROCARDIO” project (this project has received funding from the European Seventh
Framework Programme under grant agreement n° 295823).
64 | P a g e
Columbus, OH
Radiation induced carcinogenesis is one of the detrimental side effects of radiation therapy. Ionizing
radiation directly or indirectly induces DNA damage and generates various toxic lesions. It has been
proposed that mutations resulted from misrepaired DNA lesions lead to gnomic instability and play
important role in tumor initiation and progression. However, the regulation of multiple pathways in repair
radiation induced DNA damage, the effect of repair processes on genomic instability, and the role of DNA
repair in radiation induced carcinogenesis still remains to be clarified. In this review, we will focus on
recent findings on how DNA double-strand break repair machineries are affected by exposure to ionizing
radiation and during proliferation, and will discuss how repair of double strand breaks may be a key player
in the process of radiation-induced carcinogenesis.
(S1504) Abscopal effect: much more than a conceptual dichotomy. Mariateresa Mancuso, ENEA, Rome,
Italy
In the last ten years, the concept that radiation generates long-range signaling responses has been
described in a wide variety of experimental systems (in vitro, cultured artificial 3-D human tissue systems,
ex vivo models), suggesting a need for a new paradigm in radiation biology. In this scenario, our own
research activities are focused on in vivo validation of non-targeted effects, with particular attention to
implications for cancer development. From a biologist’s point of view, abscopal effects induced by
radiation include induction of genomic instability, cell death, and oncogenic transformation in normal
tissues outside the irradiated volume. Using a mouse model of radiation sensitivity, we provided the first
proof-of-principle that non-targeted (abscopal) effects are factual in vivo events with carcinogenic
potential in different tissues (i.e., CNS and skin), suggesting a key role of gap junction intercellular
communication in transmission of oncogenic radiation signals to un-hit tissues. Moreover, we established
that interplay between radiation dose and exposed tissue volume plays a critical role in non-targeted
effects, including carcinogenesis, occurring in off-target tissues. Besides this detrimental significance,
abscopal effects may also lead to beneficial consequences. In fact, from the oncologist’s perspective, the
term refers to distant tumor regression after localized irradiation, and anti-tumor abscopal effects have
been clinically well documented. Recently, we have experimentally demonstrated that abscopal effects
induced by radiation are able to sterilize non-irradiated tumor cells depending on the presence of wt p53,
raising the intriguing hypothesis that the tumor biology could have a key role in development of
personalized radiotherapy protocols. Although radiation induced non-targeted effects have been studies
mostly in terms of cancer induction, there is recent evidence from my laboratory that it is also link to
development of non-cancer effects, mainly cardiovascular. Results supporting these conceptual
dichotomies of radiation abscopal effects will be presented and discussed. Supported in part by Grant
10357 from AIRC and “PROCARDIO” project (this project has received funding from the European Seventh
Framework Programme under grant agreement n° 295823).
64 | P a g e
