Co-carcinogenic Action of Saccharin in the Chemical Induction of Bladder Cancer

Hicks, Rodney W.; Wakefield, J. St. J.; Chowaniec, J.

doi:10.1038/243347a0

Cited by 72 publications

(20 citation statements)

References 5 publications

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“…Saccharin is an agent which only just achieves any measurable carcinogenic effect when fed to rats that receive no other treatment but which has a gross carcinogenic effect when rats pretreated with the mutagen methylnitrosourea are exposed to it (Hicks et al 1973). It is perhaps unfortunate that animal feeding experiments routinely use an untreated control group but do not also routinely feed the test substance to a group of animals that have been exposed to a moderate dose of some well-known mutagen.…”

Section: Identification Of Non-mutagenic Carcinogensmentioning

confidence: 99%

Epidemiology, multistage models, and short-term mutagenicity tests

Pető¹

2016

Int. J. Epidemiol.

100

107

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This section is intended as an introduction to, and apology for, multistage models. Such models occupy a curious position in the world of cancer research. It seems likely that multistage processes underlie the generation of a large majority of human cancers (the carcinomas), yet most research workers do not have any real interest in discussing the various alternative multistage models that attempt to describe these processes. These research workers can't all be wrong, so what is wrong with multistage models? The trouble is, I suppose, that the processes usually invoked are, in principle, extremely difficult to observe (phenotypically silent changes in a few scattered somatic cells), and that very similar predictions for the few things we can actually observe may follow from mathematical elaboration of various very different multistage models (each with its own implausible chalones, feedback mechanisms, exact numbers of "stages" to be progressed through, mutations, epigenetic switches, clonal growth rates, etc.).However, laboratory investigations of various completely different aspects of the processes of cancer induction (viruses, mutagens, host control mechanisms, etc.) are already well established, and new lines of investigation, particularly of "cocarcinogenic" processes, may yet emerge. No single process is likely to be the whole truth, and we must hope that some grand synthesis of the known processes will eventually be put together which will describe all the essential features of human cancer induction. Although the eventual synthesis is not yet in sight, multistage models should at present be thought about to some extent, and their general features should be common knowledge, as the general framework of this eventual synthesis will (at least for that 90% of fatal human cancers which are carcinomas) almost certainly be some kind of multistage model. Moreover, despite all their present uncertainties, multistage models for carcinoma induction have already offered plausible answers to various questions concerning monoclonality, dose-response relationships under conditions of regular exposure, hypothetical "threshold" doses, the synergistic effects of different carcinogens, the role of luck, and, last but not least, the connection between cancer and aging. (This latter point has been only partly resolved: multistage models give a very natural explanation for cancer being a hundred times rarer among young adults than among the elderly, but no plausible explanation has yet been offered for the fact that the risk of cancer in old age is not vastly different in species with very different life-spans.)In the next three sections, I will recapitulate a few formulae that can emerge from certain multistage models.(Readers who don't like even simple algebra can pass over

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Section: Identification Of Non-mutagenic Carcinogensmentioning

confidence: 99%

Epidemiology, multistage models, and short-term mutagenicity tests

Pető¹

2016

Int. J. Epidemiol.

100

107

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“…However, neoplasms were first detected in the saccharin-treated groups (B and D) and the mean latent period was also shorter in these groups (Table XI). (Hicks et al, 1973a(Hicks et al, , 1975 or a threshold dose of FANFT (Cohen et al, 1979) produced a high incidence of tumours of the urinary bladder.…”

Section: Urine Studies and Kidney Weightsmentioning

confidence: 99%

“…50% in the diet (Taylor & Friedman, 1974;Tisdel et al, 1974;Arnold et al, 1977b). Furthermore, the administration of saccharin either in the drinking water (2 g/kg/day) or diet (4 g/kg/day) to rats previously given a single sub-carcinogenic dose of N-methyl-N-nitrosourea (MNU) produced a high incidence of bladder tumours (Hicks et al, 1973a(Hicks et al, , 1975(Hicks et al, , 1978Hicks & Chowaniec, 1977;Hicks et al, 1978). These findings suggested that saccharin could promote carcinogenesis initiated by MNU, and recent work by Cohen et al (1979) confirmed a promoting effect of saccharin on bladder neoplasia after a threshold dose of N(4-(5-nitro-2-furyl)-2-thiazolyl) formamide (FANFT).…”

mentioning

confidence: 99%

Ortho-toluene sulphonamide and saccharin in the promotion of bladder cancer in the rat

Hooson¹,

Hicks²,

Grasso³

et al. 1980

Br J Cancer

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Summary.-The importance of the contaminant OTS in the promoting activity of commercial saccharin on rat bladder neoplasia was investigated. OTS, OTS-free and OTS-contaminated saccharin were administered in the drinking water or diet for 2 years to groups of rats pretreated with an intravesical instillation of MNU; OTS alone and OTS-free saccharin were also given to groups of rats not pretreated with MNU.Administration of OTS was not associated with changes in urinary pH, crystalluria or calculus formation, had no effect on the histology of normal rat bladder, and did not increase the incidence of bladder hyperplasia or neoplasia elicited by pretreatment with MNU. No differences could be found between the effect of OTS-free or OTS-contaminated saccharin on bladders of rats pretreated with MNU. These results indicate that OTS contamination played no part in the reported promoting activity of saccharin on the rat bladder.Administration of saccharin did not increase urinary pH, crystalluria or calculus formation, and failed to promote bladder neoplasia after a carcinogenic dose of MNU, though the numbers of proliferative lesions in the bladder were increased.

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“…Much of this speculation, stems from several publications in the early 1970s, where researchers noticed the spontaneous development of urinary bladder cancer in rats that had been given excessive amounts of saccharin [2,3]. A result of these studies was the implementation of the Saccharin Study and Labeling Act of 1977, which required all foods containing saccharin to have labels indicating that the compound was a potential carcinogenic agent.…”

mentioning

confidence: 95%