Paternal Exposure to Ethylnitrosourea Results in Transgenerational Genomic Instability in Mic

Colin D. Glen (7584737)

Hiu-Pak Wong (7584743)

Karen Monger (7584740)

Peter Hickenbotham (5348219)

Ruth C. Barber (7584746)

Yuri E. Dubrova (7580975)

Leicester Research Archive

Paternal Exposure to Ethylnitrosourea Results in Transgenerational Genomic Instability in Mice

Recent data show that the effects of ionising radiation are not restricted to the directly exposed parental germ cells, but can also manifest in their non-exposed offspring, resulting in elevated mutation rates and cancer predisposition. The mechanisms underlying these transgenerational changes remain poorly understood. One of the most important steps in elucidating these mechanisms is to investigate the initial cellular events that trigger genomic instability. Here we have analysed the effects of paternal treatment by ethylnitrosourea, an alkylating agent which is known to form specific types of DNA adducts, on the transgenerational effects in the first-generation (F1) offspring of exposed CBA/Ca and BALB/c male mice. Mutation rates at two expanded simple tandem repeat loci were significantly elevated in the F1 germline of both strains. Pre- and post-meiotic exposures resulted in similar increases in mutation rate in the F1 germline. Within each strain mutation rates were equally elevated in the germline of male and female F1 offspring of the directly exposed males. The results of our study suggest that transgenerational instability is not attributed to a specific sub-set of DNA lesions, such as double strand breaks, and is most probably triggered by a stress-like response to a generalised DNA damage. 

Yuri E. Dubrova

Peter Hickenbotham

Colin D. Glen

Karen Monger

Ruth C. Barber

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Paternal exposure to ethylnitrosourea results in transgenerational genomic instability in mice. Environ

https://lra.le.ac.uk/bitstream/2381/3910/1/Dubrova%20EnvMolMutat%2008.pdf

Paternal Exposure to Ethylnitrosourea Results in Transgenerational Genomic Instability in Mice

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