CAN WE PREDICT CARCINOGENICITY?

... Small Animals And Bacteria Not Entirely Satisfactory In a life-threatening situation short courses and minimal doses of known animal carcinogens are often used for

cancer treatment in humans, when the immediate benefits are worth the long-term (10-30 years) risk of cancer.

But the safe dosage limits of any carcinogen are unknown for humans. It is not known whether all chemicals

carcinogenic in animals cause cancer in man, or whether chemicals (with the possible exception of trivalent

arsenic) carcinogenic in man also cause cancer in rats or mice. In one study only 11 of 120 suspect chemicals

were found to be, in fact, carcinogenic. 'Drugs carcinogenic in animals should be considered potentially carcinogenic in man.'

Of l 7 5 carcinogens tested in one study 157 were mutagens. In another only 14 of 108 chemicals thought to be

noncarcinogenic were found to be mutagenic. As almost all chemicals carcinogenic in humans are mutagenic,

testing for mutagenicity is a valuable screening test to cope quickly and economically with large numbers of

chemicals, and even identifying potentially dangerous chemicals in complex mixtures. However, all mutagens

are not necessarily carcinogenic.

'Drugs found mutagenic in bacterial tests should be regarded as possible carcinogens requiring animal tests. '

Two major complications in detecting carcinogenic drugs are the lengthy latent period and the fact that only

·exceptionally do carcinogenic agents cause unusual and therefore noticeable tumours, e.g. diethylstilboestrol

(vaginal carcinoma) and vinyl chloride (angiosarcomas of the liver).

Medical Letter 18: 74 (27 Aug 1976)

... Now The Opossum Takes The Stage Investigation of transplacental carcinogenesis has been renewed by the discovery that diethylstilboestrol produces

vaginal adenosis and adenocarcinoma in the daughters of mothers who take it in pregnancy, and epididymal cysts

and possibly other genital abnormalities in their sons. Studies on the more familiar laboratory animals have been

rather unsatisfactory, probably because of the short time between completion of organogenesis and functional

maturation of the reproductive system and development of immunocompetence and lymphoid system maturation.

The opossum, with its peculiar pregnancy and fetal development, is now being used to great advantage. Giving

ethyl-nitroso-urea (ENU) to the opossum while the developing animal is marsupialised and drinking maternal milk

(corresponding to the last 7-8 months of uterine development in man), produces a variety of epithelial and

mesodermal embryonic neoplasms similar to those in human infancy and childhood. The tumours thus produced

include embryonal neoplasms of the eye, liver, brain, kidney, muscle and jaw. They are often found at the same

sites as malformations, suggesting that, contrary to previous findings in laboratory animals, carcinogenesis and

teratogenicity are not exclusive, granted the appropriate stimuli. This flood of new information includes the first

experimental production ever recorded of some cancer; but the most interesting is the production, in about 30%

of animals exposed to ENU within 6 weeks of birth, of embryonal renal tumours more like those of man than any

others produced experimentally in animals.

'A powerful new technique for explaining the mysten"es of teratogenesis and embryonal carcinogenesis seems now to be available; and it and other approaches will be eagerly exploited because they touch on many features of childhood cancer that have long baffled us.'

Editorial: Lancet 2: 506 (4 Sep 1976)

INPHARMA 18th September, 1976 p3