Wednesday, February 22, 2012

Ionizing Radiation and Germ Cell Damage: Link to Autism?


Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice  Guogang Xua, C. Alex McMahanb, Kim Hildretha, Rebecca A. Garciaa, Damon C. Herberta, Christi A. Walter Mutation Research/Genetic Toxicology and Environmental Mutagenesis Available online 31 January 2012


Abstract


Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lacI transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment. 


Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle-aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation. 

This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline.

[excerpt from article]
"Advanced paternal age (about 40 years or older at the time of conception) is associated with an increased incidence of a wide range of genetic and epigenetic diseases in offspring [2]. For example de novo mutations (C to G in fibroblast growth factor receptor 2 (FGFR2) gene) in 57 Apert cases were all of paternal origin…In addition to several diseases with clear Mendelian inheritance, advanced paternal age is also linked to an increased risk for diabetes with a genetic component such as childhood cancers [5-7], diabetes mellitus type [8], multiple sclerosis [9], autism [10] and congenital malformations [11], and others. The association between paternal age and increased risk for diseases in offspring may be at least partially ascribed to mutagenesis in male gametes [12-16]."

Majia Here: Classical autism in children has been linked to father's age in a positive relationship (older father higher risk of autism in offspring)

This article on the effects of ionizing radiation suggests one mechanism. The body's susceptibility and/or capabilities to repair DNA damage from ionizing radiation wane with age, increasing the likelihood that the offspring will inherit damaged DNA.

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