A new study investigating the effect of thirdhand smoke (THS) in a mouse model system specially designed to mimic the genetic diversity of human populations has shed new light on how genetic predispositions contribute to an individual’s cancer risk.

The harm caused by the chemical residues of tobacco smoke may vary with genetics. (Credit: John Graham/iStock)

The study, published in the April Issue of Environment International, was part of a multi-year effort led by Biological Systems and Engineering Division (BSE) scientists Bo Hang, Jian-Hua Mao, and Antoine Snijders to clarify the health hazards that THS may pose to humans. Because researchers can carefully control environmental conditions and genetic background, laboratory studies using mice (which share common biological features with humans) can be powerful tools for representing the health effects of environmental exposure on people. But prior experiments have typically tested the effect of THS exposure on a single genetic strain of mouse, making results less applicable to a diverse human population.

In this study, the Berkeley Lab team worked with scientists at UC San Francisco and international collaborators to examine the effect of THS exposure on eight genetically distinct strains of mice randomly selected from the Collaborative Cross (CC) mouse model, a large collection of mouse strains with genetic diversity comparable to that seen in humans. By monitoring tumor development after THS exposure in these eight CC strains, including some with pre-existing tendencies to develop certain cancers, the researchers hoped to develop a more realistic understanding of how tobacco smoke residue could impact cancer risk in people.

The researchers found that mice housed with cigarette smoke-treated cloths for six weeks (from 4 to 9 weeks of age) had significantly more tumors than unexposed mice, with a particular increase in lung and liver tumors. This dovetails with existing evidence that THS can increase cancer incidence in mice. But the researchers also observed that different CC mouse strains showed a wide range of responses to THS exposure, implicating genetic background as a key susceptibility factor. Specifically, the two strains with known predispositions for certain cancers showed an outsize increase in tumor development after exposure to THS.

Along with the strong implication that pre-existing conditions, like those present in human populations, can influence the carcinogenic effect of THS, these findings demonstrate the power of the CC mouse model for exploring how genetic variation and environmental exposure interact. Future studies using additional CC strains could help identify the genetic mechanisms underlying THS-related health risks.

Other Berkeley Lab authors include: Lara Gundel from the Energy Technologies Area and Jamie Inman and Hang Chang from the BSE Division.