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Embryonic Exposure to Harm Reduction Tobacco Products Cause Mitochondrial and Behavioral Defects Similar to Conventional Tobacco

Abstract

Developmental toxicology is an ever-changing field dedicated to ensuring the safety and efficacy of foods, drugs and chemicals available to the public, specifically concerned with effects on a developing embryo. While many studies have uncovered the detrimental health effects of tobacco use, a concern to the health problems associated with harm reduction tobacco products (HRTPs) grows as the usage increases, specifically in women who are, or may become pregnant. Using a novel approach analyzing mitochondrial network morphology called Mitochondrial Network Analysis (MiNA), significant changes in mitochondrial network morphology were found in human embryonic stem cells (hESCs) exposed to both Camel and Camel Blue cigarettes, conventional and HRTP respectively. Supplementation with ascorbic acid led to a general improvement of network morphology for both products suggesting ROS as one mechanism of toxicity. To determine if prenatal exposure to Snus, a non-combustible HRTP, causes any increased risk of neurological damage such as anxiety and motor control, pregnant mice were injected with a Snus tobacco extract, and allowed to age into adulthood. The adult mice were then tested for such neurological issues using the elevated plus maze (EPM) and the Suok test. Results suggest female mice are more susceptible to increased behavioral issues such as anxiety and reduced motor control when exposed in utero to Snus tobacco extract than male mice compared to the untreated. This suggest that these neurological concerns may be linked in some way to the X-chromosome, and environmental toxicants such as tobacco may increase chances of occurrence. These studies together suggest that embryonic exposure to HRTPs may lead to other increased risks, not typically evaluated, that may be equal or more detrimental than conventional tobacco and must be taken into consideration when making claims of reduced harm.

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