Mouse, Rat & Cell Studies Don’t Make E-Cigarettes Carcinogenic

In determining what causes cancer in humans, epidemiologic and public health research is far superior to lab studies based on cells, mice or rats.  While the latter can provide important information about the biology of cancer, the vast majority of carcinogens have been discovered in studies of human exposures. 

Although numerous epidemiologic studies prove that smokers are more likely to contract a variety of cancers, decades of research on cells and animals have failed to establish which of the thousands of toxins in cigarette smoke cause human lung, bladder or esophagus cancer. 

Of the two major components of e-cigarette juice, we know this: Nicotine, the subject of thousands of studies, has never been shown to be a cancer-causing agent, and propylene glycol is generally recognized as safe for human use by the FDA. 

Regrettably, these facts haven’t stopped some researchers from scaremongering about e-cigarettes.  A study published in January (here) has led to a media frenzy suggesting that e-cigarette liquid may be as dangerous as smoke (here).  This is nonsense. 

Normal cells do not live forever.  But cancer cells are “immortalized” and are able to proliferate indefinitely.  The experiments reported in this study were conducted in immortalized cell cultures, which also included mutations of two important genes: p53, an anticancer gene that is active in normal cells, was “silenced”; and k-ras, a well-characterized oncogene, was “activated.” 

The researchers were essentially using a cancer cell line.  They measured the effect of two (unquantified) concentrations of nicotine e-cig solution and some sort of smoke extract on assays of growth and invasiveness after 10 days of exposure. 

Exposure of the cells to the low-nicotine e-cig solution and to the smoke extract had no effect on the invasiveness of the cells (a cancer trait).  They reported, “We will next examine the effects of high nicotine conditioned media on cell invasion,” indicating a future experiment.

The researchers noted that after 96 hours of exposure to e-cig solution, the cells showed changes in gene expression.  This is not particularly newsworthy.  Genes are the bits of DNA that tell cells what to do.  At any given time cells have many thousands of active genes.  Any environmental change can produce changes in the expression of large numbers of genes. 

In their effort to implicate nicotine, the researchers omitted information as to whether they had established appropriate experimental controls, such as exposure of the cells to other common agents such as caffeine or coffee extracts.

Cellular and molecular research explores the incredibly complicated biology of cancer, but it is of limited value in identifying carcinogens.  There are well established tests to determine if an agent is a possible mutagen, which is an indication that it might be cancer-causing.  A 2007 study of American smokeless products was essentially negative (here), which is completely consistent with epidemiologic studies.  It is likely that tests of e-cigarette liquids would produce similar results.   

Undistinguished research on smokeless tobacco products routinely generates headlines and soundbites best suited for the tabloids.  From a public health standpoint, it is shameful that researchers and media conflate vague, exaggerated and highly theoretical claims about e-cigarette juice to the very real risks of cigarettes.