Primary and secondary bystander effect and genomic instability in cells exposed to high and low linear energy transfer radiations

Abstract

Purpose: Non-Targeted effects (NTE), such as bystander effect (BE) and genomic instability (GI) challenge central dogma of radiation biology. Moreover, there is a need to understand its universality in different type of cells and radiation quality.

Materials and method: To study BE (primary and secondary) and GI Human adult dermal fibroblast (HADF) and peripheral blood lymphocytes (PBL) were exposed to low fluence of ²⁴¹Am alpha (α) particle and 6 MV X-ray. The BE was carried out by means of co-culture methodology after exposing the cells to both types of radiation and damage was measured using micronucleus assay (MN) and chromosomal aberration assay (CA) in the p1 cells while the GI was followed up in their progeny.

Results: A dose-dependent increase in DNA damages (MN and CA) was observed in directly irradiated and bystander cells. The magnitude of BE was higher (6 fold) in cells co-cultured with the α-irradiated cells than that of with X-irradiated cells. Cross exposure of both cell types confirms that radiation induced BE is cell type dependent. In addition, induced DNA damage persisted for a longer population doubling in α-particle irradiated cells.

Conclusion: This work adds evidence to secondary bystander response generated from primary bystander normal cells and its dependence to radiation quality.

Keywords:

• Primary and secondary bystander effect
• genomic instability
• 241Am α-particle
• chromosomal aberration and micronucleus

Acknowledgments

The authors thank Dr. Chinnadurai Mani, Department of Cell Biology and Biochemistry, Texas Tech University Health Science Center, Lubbock, Texas, USA, and Prof. Edourad Azzam, Department of Radiation Oncology, Rutgers State University, NJ, USA for their technical input and editing. Dr. G. Tamizh Selvan Department of Biochemistry, NITTE, Mangaluru, India, and Ms. Sidonia Valas, Dr. Kamashi Memorial Hospital, Chennai, for her kind help in assisting irradiation and technical support.

Disclosure statement

All the authors declare there is no conflict of interest.

Additional information

Funding

The authors sincerely acknowledge the financial assistance from Atomic Energy Regulatory Board Government of India. Grant Number (AERB/CSRP/Proj. No. 58/04/2014) and CSIR (Council of Scientific and Industrial Research, Government of India (File. No. 09/949/0005/18-EMR-I).

Notes on contributors

K. Kanagaraj

K. Kanagaraj is a CSIR-Senior Research Fellow, currently working on the Relative Biological effects and genomic instability of High LET radiation using cytogenetics markers.

V. Rajan

V. Rajan is a scientific assistant at Bhabha Atomic Research Centre, Mumbai, currently working on alpha particle induced bystander effects.

Badri N. Pandey

Badri N. Pandey is Scientist ‘G’, Head, Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre. His area of work is on the radiation on signalling in cancer cells.

K. Thayalan

K. Thayalan is Head, Medical Physics, Department of Radiation Oncology, at Dr.Kamashi Memorial hospital, Chennai.

P. Venkatachalam

P. Venkatachalam is a Professor in Human Genetics, currently working on Radiation biodosimetry, Biological effects of low dose radiation and RBE of alpha particle radiation.