aetiology – the scientific study of the causes of disease (spelt etiology in the United States)

question received

 

Does mutagenic always imply carcinogenic, and if so, why? If it is true, it would seem to imply that all mutations are damaging.

 

response

Does mutagenic always imply carcinogenic, and if so, why? If it is true, it would seem to imply that all mutations are damaging.

14th November 2024

Not all mutations will be carcinogenic. Cancer is the result of cells (initially perhaps just one cell) breaking free from the normal control mechanisms in the body and beginning a sequence of cell divisions and migration. Cancer is now viewed as a genetic disease, and is caused by changes in genes that are intimately concerned with the control of the cell cycle. Mutational changes in other genes will not necessarily induce cancerous behaviour.

I believe it is fair to say that most mutations will be damaging, but not all. After all, if you have a finely tuned and incredibly complex system, apparently random changes in important control systems are more likely to reduce its ‘fitness’ than enhance it. However, evolution is dependent on mutations as a source of variation that can then be tested by the process of natural selection. Most of the mutant organisms will fall by the evolutionary wayside – indeed many mutations are lethal during the embryonic phase of development – but just a tiny minority will be in a better position to survive and reproduce than the original form, handing on the beneficial mutation to their own offspring. So some mutations are beneficial to the organism. Think of the amazing and rather worrying ability of micro-organisms to become resistant to antibiotics.

Large genomes are particularly at risk of mutations, and a fascinating array of protective processes have evolved to protect organisms against their effects:

 each cell checks its own ‘health’ before cell division  if genetic errors are detected during this checking process, several strategies are available for DNA repair  if irreparable internal faults are detected, a process called apoptosis (in which cells quietly close down) is set in motion  there is diploidy (2 sets of genetic information per cell, one from Mum and one from Dad)  at the whole-organism level, sexual reproduction with mate choice also reduces the effects of harmful mutations.

In recent years, there has been convergence of knowledge from several fields of research to produce a better understanding of carcinogenesis. This is well reviewed in a special edition of Scientific American (September 1996). Essentially, it is now known that mutations in certain controlling genes (eg: proto-oncogenes and tumour suppressor genes) can result in cells ignoring control signals from outside, and ignoring warnings from internal checking processes. Thus, in a cancer cell, processes that should result in apoptosis are blocked and the cell sets off on its antisocial programme of cell division and migration.