Smoking Linked To Gene Damage Over 3 Generations

A study released Wednesday in Plos Biology shows that some effects of dad’s nicotine use can get passed onto his kids — and to some degree to his grandkids. Pradeep Bhide, Ph.D., director of the Center for Brain Repair at the Florida State University College of Medicine, led a team of scientists who showed that the cognitive effects of nicotine use persisted through three generations of male mice.
In the FDA’s current tobacco warnings, Bhide tells Inverse, there’s “nothing about men smoking at any time.” His paper suggests it’s time for that to change.

Nicotine Derails Generations of Brains

The link between a mother’s nicotine use and cognitive issues like ADHD in her children has been well established, and a few previous analyses of existing data presented a “hint” that a father’s smoking could cause the same issues in his kids, says Bhide. The new study, however, is the first to demonstrate that the link is a robust phenomenon.
In the experiments, Bhide’s team gave 12 male mice nicotine-laced water during the period when they were producing sperm, then mated those mice with females that hadn’t been exposed to nicotine. The kids all showed characteristics like hyperactivity, attention deficit disorder, and cognitive inflexibility, which were tested using tricky mouse tasks called the Barnes Maze and the Y-Maze.
Using females from this generation of mice, the team induced mating with males from a separate, nicotine-free group. Once the babies from that generation grew up, it was clear that the cognitive effects had persisted yet again, but to a lesser degree.


Clearly, nicotine-induced changes in the original “grandfather” DNA were being passed on through the generations, which means that those changes had to be present in the DNA of his sperm. When the team looked at the sperm from the original males, they saw that multiple genes carried “epigenetic modifications” — impermanent physical changes to the DNA that make certain genes more or less usable. They’ve been referred to by scientists as “ornaments on a Christmas tree.” We don’t know the answers to all those things. One of the genes affected by epigenetic modifications was the dopamine D2 gene, which is implicated in brain development and learning. The team’s hypothesis is that these epigenetic changes, induced by nicotine exposure, were passed on through the original generation’s sperm into the children of the next. The changes persisted to some degree in the DNA of those children, so it’s possible some “decorations” were removed from the DNA Christmas tree, which is why the cognitive problems weren’t as robust in the final generation.