Chromothripsis And Epigenomics Complete Causality For Cannabis

And Addiction-Connected Carcinogenicity, Congenital Toxicity And Heritable Genotoxicity

Albert Stuart Reece, Gary Kenneth Hulse

Extracts from the above research.  Recommend readers go to source for complete study.

A B S T R A C T

The recent demonstration that massive scale chromosomal shattering or pulverization can occur abruptly due to errors induced by interference with the microtubule machinery of the mitotic spindle followed by haphazard chromosomal annealing, together with sophisticated insights from epigenetics, provide profound mechanistic insights into some of the most perplexing classical observations of addiction medicine, including cancerogenesis, the younger and aggressive onset of addiction-related carcinogenesis, the heritability of addictive neurocircuitry and cancers, and foetal malformations.

Tetrahydrocannabinol (THC) and other addictive agents have been shown to inhibit tubulin polymerization which perturbs the formation and function of the microtubules of the mitotic spindle. This disruption of the mitotic machinery perturbs proper chromosomal segregation during anaphase and causes micronucleus formation which is the primary locus and cause of the chromosomal pulverization of chromothripsis and downstream genotoxic events including oncogene induction and tumour suppressor silencing.

Moreover the complementation of multiple positive cannabis-cancer epidemiological studies, and replicated dose-response relationships with established mechanisms fulfils causal criteria. This information is also consistent with data showing acceleration of the aging process by drugs of addiction including alcohol, tobacco, cannabis, stimulants and opioids. THC shows a non-linear sigmoidal dose-response relationship in multiple pertinent in vitro and preclinical genotoxicity assays, and in this respect is similar to the serious major human mutagen thalidomide. Rising community exposure, tissue storage of cannabinoids, and increasingly potent phytocannabinoid sources, suggests that the threshold mutagenic dose for cancerogenesis will increasingly be crossed beyond the developing world, and raise transgenerational transmission of teratogenicity as an increasing concern.

CONCLUSION

As mentioned above high dose cannabis and THC test positive in many genotoxicity assays, albeit often with a highly non-linear threshold like effects above low doses. As long ago as 2004 it was said that 3–41% of all neonates born in various North American communities had been exposed to cannabis [172]. Since cannabis is addictive [187], is becoming more potent [77,83,86], quickly builds up in adipose tissues [62,82] and seems generally to becoming more widely available under fluid regulatory regimes [187,188], real concern must be expressed that the rising population level of cannabinoid exposure will increasingly intersect the toxic thresholds for major genotoxicity including chromosomal clastogenicity secondary to interference and premature aging of the mitotic apparatus.

Under such a conceptualization, it would appear that the real boon of restrictive cannabis regimes [189] is not their supposed success in any drug war, but their confinement in the populations they protect, to a low dose exposure paradigm which limits incident and transgenerational teratogenicity, ageing, mental retardation and cancerogenicity.

Source:   Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Journal Homepage: www.elsevier.com/locate/molmut    January 2016

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