5.4 The Ames Test

>Does anyone know more about this Ames test?

The Ames test cultures mutations of bugs (usually Salmonella spp) that are unable to grow without the amino acid histidine and adds suspected mutagens to the culture medium (after incubating them with liver extract to expose them to lysosymal activity). If the bugs then grow, the mutation is deemed to have reversed (ie they now synthesise histidine) and the test substance is regarded as (ultimately) mutagenic. It is the case that the majority of known chemical carcinogens are also mutagens according to the Ames Test.

The problem is that also according to the Ames Test the prevalence of environmental mutagens is so high that the human population should long ago have been wiped out by cancer if the extrapolations were correct. (The extrapolations being histidine gene mutagenicity equals ultimate carcinogenic action, and salmonella bugs equals people.) This is of course acknowledged by pathologists - but seems not to be understood by the rank and file scare mongers who like to appear to be *scientific* in their attacks on herbalism.

jonno.teleport.com (Jonathan Treasure)

From: Kevin Jones <100621.17.CompuServe.COM>

There are several drawbacks to the Ames test which basically make it worthless on its own.

Firstly carcinogens are divided into those which require to be metabolised in a cell (activated) and those which don't. Obviously the metabolism of a bacterial cell is going to differ from that of a mammalian cell. Compounds which are activated in a bacterial cell may therefore show no activity in a mammalian cell and vice versa.

Secondly carcinogens act by reacting with genetic material. The type which are metabolically activated generally form free radicals which then react with DNA. Many carcinogens have an affinity for a specific sequence of nucleotides. Obviously the number of sequences that are shared between mammals and bacteria are going to be very small! There may well be many chemicals which cause mutations in bacteria but which have absolutely no effect on mammals.

In short, all the Ames test does is show that a chemical produces a mutation in Salmonella bacteria. It might possibly indicate the potential for being carcinogenic in higher organisms - and then again it might not. It also is quite possible that the Ames test could declare a chemical safe which is quite powerfully carcinogenic in mammals simply because it does not affect bacteria.

In any case, relying on the Ames test shows a distinct lack of understanding of the nature of cancer and cell growth. Mammalian cells are programmed to die. Only chemical messages keep them alive and keep a particular gene turned off. It's like a dead man's handle. The moment a genetic error is detected the cell is told to stop dividing. If the error is serious, this gene is turned on and the cell destroys itself. This gene and its backup copy have to fail before a cancer can develop _or_ the chemical messenger system has to become defective and keep it turned off _or_ the self-checking mechanism has to become defective. Many cancers have genetic defects in one or more of these command chains. Presumably it is also possible for an error to develop in the signalling system between the self-destruct gene and the lysosome - the dead man's handle is released but the grenade doesn't go off.

Another gene which codes for ras protein is part of the cell division mechanism. If it is defective the cell goes on dividing. Similarly other parts of the cell division command chain (growth hormone receptor, cytokines etc) can have errors. Some viruses (eg: Epstein-Barr in some circumstances) cause a proliferation of growth hormone receptor on the cell's surface which keeps the cell dividing. The more a cell divides, the more the chance of a mistake and therefore the higher the risk of a cancer developing.

Now the likelihood of being able to show that these specific genetic defects are going to be caused in humans from a bacterial model is laughable. A bacterium is a single-celled organism. It has no use for programmed cell-death!

The Ames test may have some value as an initial screening test, but only as long as its limitations are acknowledged. To rely entirely on it as definite proof that a compound is carcinogenic is not only laughable - it is also bad science!