To PJ:
Your central question was ( I think) "Show me evidence that carcinogens block the oxidative phosphorylation pathway". I had confined my comment to one of the cytochrome complexes, but there are probably other vulnerable sites as well in this pathway, actually.
The discovery began in 1912 when Prof William Koch discovered that completely parathyroidectomised dogs produced guanidine and methyl guanidine in the tissues increasingly until the levels became fatally in excess. At the same time he noticed excess lactic acid, calcium and phosphate was eliminated from the animals. From this he deduced the chemistry of guanidine was to activate its amine group by its conjugation with an imide group; - but also there was a tendency to deactivate this amine group by such substitutions as acetic acid as in creatine, and amino-valeric acid in arginine. Guanidine and methyl guanidine are highly toxic carcinogens while creatine and arginine are not.
The large elimination of lactic acid (even though the lungs were well ventilated) gave him the insight that metabolism was being blocked somewhere, so that only glycolysis was occurring in the metabolism, hence the excess lactate. He then pinpointed this to the carbonyls which, being good dehydrogenators, provide the first step in oxidation (carbonyl groups are of course present in ubiquinone or any quinone for that matter). I don’t think at that time ubiquinone had been discovered so the insight was a very good one.
The idea that carcinogens caused faulty metabolism was later taken up by Otto Warburg, and after that by Szent Gyorgii, who proposed in the early 1960s that the only way to deal with the cancer problem was to restore metabolism and that this could be achieved using quinones. The Hungarian group who produce Avemar are following up the ideas of Szent Gyorgii with spectacular success. We are developing Koch’s ideas and testing various quinones in vitro, some way behind them, but with a broader approach.
A modern example of the attack on the mitochondrial metabolism is the carcinogen vinyl fluoride.
VF alkylates the prosthetic heme group of cytochrome P-450, and the alkylate has been identified as N-(2-oxoethyl)protoporphyrin IX. This observation suggests a reaction of heme with fluoroacetaldehyde (Ortiz de Montellano et al. 1982, cited in Cantoreggi and Keller 1997).
It also is likely that incorporation of fluoroacetate into the citric acid cycle disrupts energy metabolism and leads to increased production of mitochondrial acetylcoenzyme A and hence excretion of ketone bodies and free fluoride. Administration of VF has been shown to increase acetone exhalation by rats (Filser et al. 1982).
The Filser reference is below:
Filser, J.G., P. Jung, and H.M. Bolt. (1982). Increased acetone exhalation induced by metabolites of halogenated C1 and C2 compounds. Arch Toxicol 49:107-116.
This is only one illustration of a carcinogenic attack on the metabolic pathway in the mitochondria, but as I said, if you give me your address I will send you the complete biochemistry as worked out by Koch and Szent Gyorgii, and developed further by our lab, since it is time consuming to set this out in any real detail via a post.
I see that while preparing this post several other useful and constructive critical comments have appeared, and I will try to answer these over this week end since I am invited to Cambridge for a college dinner tomorrow night, and will be out all day.
Briefly, on your other point, if the electric power utilities had to acknowledge their product was hazardous to health they would face huge lawsuits from victims and owners of property near lines, (because it can be shown they were aware of this hazard and deliberately covered it up, so they cannot plead a "state of the art" defence, Cleopatra) and enormous costs of resiting lines or buying wayleaves. I thought that was obvious: they have the example of the tobacco companies staring them in the face.