The rule: chemical and biological toxins work synergistically with inadequate nutrition in the etiology of diseases from tooth decay and the common cold to cancer

A speculative hypothesis based on Arch. Pathol. Lab. Med.—Vol 136, March 2012, 262-7. Bharat Jasani and Allen Gibbs.

The role of inadequate nutrition in weakening our bodies’ defenses to chemical and biological toxins, and in reprogramming gene expression patterns, is so obvious that most scientists forget to mention it. Yet it is so easy to nourish oneself properly: Just one Square Meal a Day. Imagine just picking up complete whole foods’ nutrition in a neat package in the grocery store. What are we waiting for?

Examples of chemical and biological toxins working synergistically are legion: HCV + alcoholism -> cirrhosis. HBV + aflatoxin -> hepatocellular carcinoma. Sucrose + cariogenic bacteria -> caries. Gum mucosal injury + “harmless” bacteria -> periodontal disease and its many sequelae. Stomach mucosal injury + “harmless” bacteria -> stomach ulcer.

In the case of malignancy: When multiple toxins work together, they can produce malignancy considerably faster than either working by itself. Since cancer is clonal, this requires that both types of toxins attack the same cell, either simultaneously or -more likely- at different times. How likely is either scenario, given 100 trillion cells and a limited lifetime supply of chemical and biological toxins? The answer probably lies in differential vulnerability. When a toxin weakens a cell, it increases its vulnerability to other toxins. The more damaged a cell, the more vulnerable it becomes, until it either dies from its wounds, commits suicide (apoptosis), or becomes “immortalized.” A powered-down cell (such as a cell whose respiration has been impaired by viruses or chemicals) is likely to be especially vulnerable to further assaults from chemical toxins and viruses or other biological toxins (cf. The Square Meal Diet, §5).

If the above is correct, then in most cases of malignancy, both chemical and biological toxins are at work. The simpler causal model, favored by the rival camps of chemical oncologists and cancer virologists, is disfavored kinetically, implying that a sufficient population of cells have been attacked by both biological and chemical toxins (not counting pseudo-viruses that may be in the germ-line) to make the multiple hit model by two distinct types of toxins more favorable overall.

Now for the asbestos story:

Significantly, even in those people exposed to the highest doses of asbestos, only 10-20% developed malignant mesothelioma (MM). In addition, about 20% of those who developed MM were not even exposed to asbestos. These data do not fit the model in which asbestos “causes” MM. At best, asbestos was a cofactor in the development of MM. What might have been the other factors? The authors speculate that one factor might have been SV40. Together, they could have produced cancer considerably faster than high doses of asbestos alone.

The simian polyoma virus SV40 may have contaminated as many as 30 million people in the US (~10% of the current population infected) who were inoculated with the polio virus in the late 1950s and early 1960s.

However, we harbor at least two prevalent (>70% infected) human polyoma viruses, BKV and JCV. If polyoma virus is a cofactor in asbestos carcinogenesis, either of these –or another one yet to be discovered- could be it. The authors may be right about SV40, but in view of the prevalence, well-documented infectivity, and the diseases known to be associated with the human polyoma viruses, there is little call to speculate about the role of the less prevalent and presumably less infectious and virulent monkey virus.

Indeed, although direct intra-pleural inoculation of SV40 produced 100% mesotheliomas in baby Syrian golden hamsters (Cicala C, Pompetti F, Carbone M. SV40 induces mesotheliomas in hamsters. Am J Pathol. 1993;142(5):1524–1533), most virologists believe that SV40 is not carcinogenic to humans. (J Clin Oncol. 2006 Sep 10;24(26):4356-65. Is there a role for SV40 in human cancer? Poulin DL, DeCaprio JA).

But what if the people harboring SV40 also have weakened target cells, weakened immune systems, and/or are exposed to one or more potent mutagens?

If SV40 by itself were strongly carcinogenic to humans, we would already have seen an epidemic of cancer in the US because of the millions of people were inoculated with this virus in the US, and thus exposed for up to 50 years, which is more than twice the normal incubation period for tumors to develop, following potent carcinogenic exposure.

Paired with one or more mutagens like asbestos, asbestos-like fibers, radiation, or tobacco smoke, however, either human polyoma viruses or SV40 might be sufficiently carcinogenic. The infectivity, integration potential, and expression of polyoma virus genes could be altered by the presence of a potent mutagen and/or immuno-compromisers and/or target cell compromisers.

Likewise, chemical mutagens alone are “slow” (latency periods of 20+ years) carcinogens because they must in general (1) activate a single copy of a sufficient number of oncogenes, (2) activate a single copy of an immortalizer gene like telomerase, (3) inactivate the first copy of a sufficient number of tumor suppressor genes, and then (4) inactivate the second copy of the same tumor suppressor genes.

However, with sufficient expression of polyoma virus proteins, particularly large “T” antigen and small “t” antigen, perhaps aided at one or more stages by the mutagenic action of asbestos and/or tobacco use, step (1) is abetted, and steps (3) and (4) are effectively bypassed, because the inhibition of tumor suppressors (p53 and pRb) are at the level of the proteins. Thus, working synergistically, the mutagen plus polyoma virus would accelerate the rate of tumorigenesis. Tumors from this synergistic process would have appeared before cancer would have appeared from the mutagen alone, possibly explaining why -at least in part- 80-90% of people exposed to the highest levels of asbestos did NOT develop MM during their “natural” lifespans.

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