Mutation Research, 244 (1990) 77
77
Elsevier MUTLET 0361
Series: 'Current Issues in Mutagenesis and Carcinogenesis' (Accepted 17 January 1990)
No. 17 The paper that follows, by Benigni, is longer than is usually published in this section of the Journal, but the issues raised therein justify this exception. The process of refereeing the paper by Benigni was turning into a private debate between 5 people so it was decided to proceed with its publication, such an extensive debate suggesting that it contained concepts worthy of debate. Two papers on the NTP database have indicated that genotoxic rodent carcinogens are capable of inducing tumours in tissues that are not sensitive to the action of putatively non-genotoxic carcinogens [Ashby and Tennant, 1988 (see p. 92) and Ashby et al., 1989 (see p. 95)]. Those analyses have been extended to include consideration of bioassay doselevel (Brown and Ashby, 1990, preceding paper in this issue of the Journal). Using the concepts developed in these 3 papers both genotoxic a n d / o r non-genotoxic carcinogenic activity has been predicted for 44 chemicals currently being tested for carcinogenicity by the NTP (Tennant et ai., 1990). Benigni has reanalysed the original assertion that there is a relationship between sites of carcinogenesis and genotoxicity, and has concluded that it is at best a weak relationship. This presents the apparent conflict - - the observation that
Correspondence: Dr. John Ashby, ICI Plc, Central Toxicology Laboratory, Alderley Park, Macclesfield, Ches. SK10 4TJ (Great Britain).
a m o n g 264 agents tested for carcinogenicity by the U.S. NTP, 16 tissues are only subject to carcinogenicity by agents that are structurally alerting and mutagenic to Salmonella, and the observation that there is no useful correlation between sites of carcinogenesis and mutagenicity to Salmonella. This section of the Journal was initiated for the discussion of such apparent conflicts.
J. Ashby
ICI PIc, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire (Great Britain)
Refe,..~ces Ashby, J., and R.W. Tennant (1988) Chemical structure, Salmonella mutagenicity and extent of carcinogenicityas indications of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NC1/NTP, Mutation Res., 204, 17-115. Ashby. J., R.W. Tennant, E. Zeiger and S. Stasiewicz (1989) Classification according to chemical structure and sites of carcinogenesis among 226 chemicals evaluated for carcinogenicity by the U.S. NTP, Mutation Res., 223, 73-103. Brown, L.P., and J. Ashby (1990) Correlations between bioassay dose-level, mutagenicity to Salmonella, chemical structure and sites of carcinogenesis among 226 chemicals evaluated for carcinogenicity by the U.S. NTP, Mutation Res. 244, 67-76. Tennant, R.W., J. Spalding, S. Stasiewicz and J. Ashby (1990) Prediction of the outcome of rodent carcinogenicity bioassays currently being conducted as 44 chemicals by the National ToxicologyProgram, Mutagenesis, 5, 3-14. Communicated by F.H. Sobels
0165-7992/90/$ 03.50 © 1990Elsevier Science Publishers B.V. (Biomedical Division)
77
Elsevier MUTLET 0361
Series: 'Current Issues in Mutagenesis and Carcinogenesis' (Accepted 17 January 1990)
No. 17 The paper that follows, by Benigni, is longer than is usually published in this section of the Journal, but the issues raised therein justify this exception. The process of refereeing the paper by Benigni was turning into a private debate between 5 people so it was decided to proceed with its publication, such an extensive debate suggesting that it contained concepts worthy of debate. Two papers on the NTP database have indicated that genotoxic rodent carcinogens are capable of inducing tumours in tissues that are not sensitive to the action of putatively non-genotoxic carcinogens [Ashby and Tennant, 1988 (see p. 92) and Ashby et al., 1989 (see p. 95)]. Those analyses have been extended to include consideration of bioassay doselevel (Brown and Ashby, 1990, preceding paper in this issue of the Journal). Using the concepts developed in these 3 papers both genotoxic a n d / o r non-genotoxic carcinogenic activity has been predicted for 44 chemicals currently being tested for carcinogenicity by the NTP (Tennant et ai., 1990). Benigni has reanalysed the original assertion that there is a relationship between sites of carcinogenesis and genotoxicity, and has concluded that it is at best a weak relationship. This presents the apparent conflict - - the observation that
Correspondence: Dr. John Ashby, ICI Plc, Central Toxicology Laboratory, Alderley Park, Macclesfield, Ches. SK10 4TJ (Great Britain).
a m o n g 264 agents tested for carcinogenicity by the U.S. NTP, 16 tissues are only subject to carcinogenicity by agents that are structurally alerting and mutagenic to Salmonella, and the observation that there is no useful correlation between sites of carcinogenesis and mutagenicity to Salmonella. This section of the Journal was initiated for the discussion of such apparent conflicts.
J. Ashby
ICI PIc, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire (Great Britain)
Refe,..~ces Ashby, J., and R.W. Tennant (1988) Chemical structure, Salmonella mutagenicity and extent of carcinogenicityas indications of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NC1/NTP, Mutation Res., 204, 17-115. Ashby. J., R.W. Tennant, E. Zeiger and S. Stasiewicz (1989) Classification according to chemical structure and sites of carcinogenesis among 226 chemicals evaluated for carcinogenicity by the U.S. NTP, Mutation Res., 223, 73-103. Brown, L.P., and J. Ashby (1990) Correlations between bioassay dose-level, mutagenicity to Salmonella, chemical structure and sites of carcinogenesis among 226 chemicals evaluated for carcinogenicity by the U.S. NTP, Mutation Res. 244, 67-76. Tennant, R.W., J. Spalding, S. Stasiewicz and J. Ashby (1990) Prediction of the outcome of rodent carcinogenicity bioassays currently being conducted as 44 chemicals by the National ToxicologyProgram, Mutagenesis, 5, 3-14. Communicated by F.H. Sobels
0165-7992/90/$ 03.50 © 1990Elsevier Science Publishers B.V. (Biomedical Division)
