Book/Book Chapter
Cooperative programme on short-term assays for carcinogenicity in Japan
Kawachi, T; Yahagi, T; Kada, T; Tazima, Y; Ishidate, M; Sasaki, M; Sugiyama, T
International Agency for Research on Cancer
EMICBACK/37325
Molecular and cellular aspects of carcinogen screening tests
INT AGENCY RES CANCER
is a chapter of
2533003 Molecular and cellular aspects of carcinogen screening tests
The short-term test has been considered to be the most practical method for the rapid screening of carcinogens.
Under a project of the Ministry of Health and Welfare, 182 compounds were examined by short-term tests over six years (1973-1978), using Salmonella typhimurium TAlOO and TA98 (mutations), Bacillus subtilis (rec assay), hamster lung fibroblast cells (chromosome aberrations, sister-3 23-324 KAWACHI ET AL. chromatid exchanges), human embryo fibroblasts (chromosome aberrations, sister chromatid exchanges), bone-marrow cells (chromosome aberrations in vivo) and silk worms (mutations).
Compounds were selected by a research group organized by the Ministry and included carcinogens, noncarcinogens and compounds not previously tested for carcinogenicity. They were selected from the following categories: (1) structural analogues of known carcinogens; (2) food additives widely used in Japan; (3) drugs administered for long periods to patients; and (4) industrial intermediates with a high annual production. The object of the programme is not to screen possible carcinogens in our environment but to improve the tests and to investigate the validity of newly developed rapid screening techniques.
Data from short- term assays for carcinogenicity are shown in Table 1: all data c ited as 'Salmonella test' are from the Salmonella/microsome assay system. Rec assays performed during 1973 did not include metabolic activation; however, from 1975-1978, a metabolic activation system was included. The chromosome aberration test in hamster fibroblasts in vitro included a metabolic ac tivation system between 1977 and 1978: among 65 compounds tested in this way, chlorpyrifos, cochineal and Eulan
U-33 were the only ones t hat required metabolic activation. The chromosomal aberration test in human fibroblasts and the sister chromatid exchange assay in human fibroblasts and hamster fibroblasts were not activated metabolically.
The validation of the short- term assays is summarized in Table 2. In the Salmonella/microsome test, of 49 compounds that showed mutagenic activity, 33 (67%) were found to be carcinogenic. On the other hand, of 66 nonmutagenic compounds, 48 (73%) were noncarcinogenic. Detailed data from the Salmonella/microsome tests are given in Table 3. Results from a combination of the Salmonella/microsome test and the chromosome aberration test (in vitro, in vivo) showed better validity than other combinations of short- term assays.
Montesano, R; Bartsch, H; Tomatis, L
IARC Scientific Publication No. 27
Proceedings of a meeting organized by IARC and the Commission of the European Communities
Hanover, West Germany
June 4-9, 1979