Formaldehyde: Another hormesis-inducing chemical

Formaldehyde (FA) is a naturally-occurring compound, produced endogenously in diverse living organisms. It also occurs widely in the environment due to anthropogenic (e.g. used as a chemical intermediate) and natural sources (e.g. a component of the volatile organic compounds blends emitted by plants). While FA is considered a potential carcinogen, living organisms have the ability to cope with FA, and some minimum endogenous levels of FA may be required for health. Recently, genetic engineering approaches transferring biological information from one organism to another led to increased assimilation of and conferred genetic-based tolerance to FA in plants-microorganisms systems. Here, we propose that FA commonly induces hormesis, a hypothesis that we confirm by collating evidence from various published studies with animals, plants, and microorganisms. The stimulation by low doses below the no-observed-adverse-effect-level (NOAEL) was modest in magnitude, in agreement with the general hormesis literature. In plants, among the endpoints showing hormesis were growth, lipid peroxidation, and photosynthetic pigments. In various animal cells, hormesis was observed in cell proliferation and viability, responses that were related to mechanisms, such as activation of phosphorylated ERK (extra-cellular signaling-regulated kinase) expression, acceleration of the process of cell division, and enhancement of the Warburg effect (i.e. use of glycolysis by tumor cells to produce energy for rapid growth). Hormetic in vitro responses were reported in several cancerous/tumorous cell lines, suggesting that FA has the potential to influence tumor promotion within a specific concentration range and biological context. These observations suggest that FA commonly acts in an hormetic manner with implications for study designs across a broad range of biological models and in the assessment of environmental and human risks associated with FA exposures.