Thirdhand Smoke Exposure: Some Are More Vulnerable Than Others

A team of researchers from Lawrence Berkeley National Laboratory, UC San Francisco and Nanjing Medical University have observed that the negative effects of thirdhand smoke exposure varied with the genetic makeup of mice.  These findings suggest that some people may be more vulnerable to the health effects of thirdhand smoke exposure than others.

By Leta Dickinson

July 22, 2021

Mice are commonly used in biomedical research as a model for humans. They often respond similarly to humans, but their responses are much less variable than those seen in humans. It is our very variability and unpredictability that gives rise to the most exciting questions in science. For example: Does thirdhand smoke affect everyone in the same way? Or are some people more vulnerable to the harmful effects of exposure?

Researchers from Lawrence Berkeley National Laboratory, UC San Francisco and Nanjing Medical University addressed this question in their latest study. They exposed six genetically distinct “strains” of mice to thirdhand smoke and then assessed if the exposure had any effect on memory and anxiety levels of the mice. They used the different strains of mice to mimic human variability, allowing the researchers to investigate how our genes may play a role in the effects of thirdhand smoke exposure on human health.

The six strains of mice in question were Collaborative Cross (CC) mice, an assortment of selectively bred mice with thoroughly studied genetic material. CC mice are frequently used in research that aims to model human genetic diversity because including many strains of CC mice in a study replicates the complexity and variety seen in a human population. This study tested six CC strains that have low, medium, and high vulnerability to anxiety.

For six weeks, the mice were kept in an enclosure with a thirdhand smoke-exposed piece of cloth or an enclosure free of thirdhand smoke. At the end of the six weeks, the mice underwent two tests: an anxiety test and a memory test. Both tests involve a light and dark box connected by a small opening.

In the anxiety test, a mouse is free to roam around the boxes while its movements are tracked. Less anxious mice are more likely to freely explore the lit box, while anxious mice spend more time in the dark box. The researchers tracked seven factors, such as the amount of time spent in the lit box or hesitation in crossing between boxes, and integrated these seven aspects into a single anxiety risk score. Thirdhand smoke researcher Dr. Hang Chang of the Lawrence Berkeley National Laboratory explains that while other studies have included one or only a few measures of anxious behavior, incorporating so many different measures produced a more accurate and nuanced representation of anxiety.

The memory test, using a similar setup, involved two trials separated by three days. A mouse is first placed in the lit box. After some delay, the door to the dark box opens, and when the mouse enters the dark box, it receives a mild footshock. When the trial is repeated after three days, mice with better memory will be less likely to run to the dark box, while mice with worse memory may have forgotten the previous experience and will quickly return to the dark box.

The results of these two tests were compared between thirdhand smoke-exposed and unexposed mice of the same strain and between mice of different strains. The researchers found that the anxiety levels of three of the six mice strains were affected by the thirdhand smoke—the female mice from two strains had decreased anxiety, and females from one strain had increased anxiety. Males and females from one strain of mice displayed significantly worse memory after thirdhand smoke exposure.

Dr. Antoine Snijders of the Lawrence Berkeley National Laboratory explains what these strain-specific results might mean. “What this really shows is that genetic background plays a very important role in assessing thirdhand smoke risk,” he says. “One person may have a very different response from another person, even at the same level of exposure.”

While this study was a first step towards unearthing the genetic component of thirdhand smoke exposure, many questions remain. Dr. Snijders stresses that the next step would be further studies of thirdhand smoke with more strains of mice to represent more genetic variety. “This analysis has only six strains,” he says. “But if you were to do this with 30 strains, you could investigate the genetic underpinnings of this effect and also more closely investigate sex specific effects that we observed.”

Thirdhand smoke interacts with our bodies in a complicated and poorly understood manner. While further studies are needed to fully understand the mechanism and who might be at the most risk, the current knowledge of thirdhand smoke is enough to safely conclude that no level of thirdhand smoke exposure is safe.

Click here to read the research study.

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