JANUS CARCINOGENS AND MUTAGENS

Janus carcinogens are carcinogenic agents that, under differing condit ions of cell type or dose, can instead act as anticarcinogens. Studies by Haseman and Johnson [J.K. Haseman, F.M. Johnson, Analysis of roden t NTP bioassay data for anticarcinogenic effects, Mutat. Res., 350 (19 96) 131-142], have demonstrated that many chemicals that are carcinoge nic for one tissue type can have anticarcinogenic action on another ti ssue type. As Magni et al. [G.E. Magni, R.C. von Borstel, S. Sera, Mut agenic action during meiosis and antimutagenic action during mitosis b y 5-aminoacridine in yeast, Mutat. Res., 1 (1964) 227-230] have shown in 1964, this principle holds true for chemical mutagens as well, that is 9-aminoacridine is an antimutagen in the vegetative cell and a mut agen in the sporulating cell. The conclusion can be drawn that two est ablished carcinogens, tobacco and ionizing radiation, are indeed Janus carcinogens. In their review of 'ambiguous carcinogens' (their name), Weinberg and Storer [A.M. Weinberg, J.B. Storer, Ambiguous carcinogen s and their regulation, Risk Anal., 5 (1985) 151-156], pointed out tha t tobacco can be classified as an ambiguous carcinogen. The strong car cinogenicity and anticarcinogenicity of tobacco smoke and/or tobacco i tself (i.e., chewing tobacco) may be due to components in the mixture, not that of a single carcinogenic chemical that also may be anticarci nogenic. Kondo [S. Kondo, Health Effects of Low-Level Radiation, Kinki Univ. Press, Osaka, Japan and Medical Physics Publishing, Madison, WI , 1995, 213 pp.] has compiled data that demonstrate that human populat ions who survive exposures to ionizing radiation generally live longer and have less cancer than unirradiated human populations, and this Ja nus phenomenon goes beyond the more trivial concept of increased sensi tivity to radiation of rapidly dividing tumor cells. Thiabendazole is an interesting compound in that it is both aneugenic and antimutagenic , and yet it does not appear to be a carcinogen or a mutagen. It is di scussed here because aneugenesis and antimutagenesis are at extremes o f the mutagenic spectrum. In general, mutagenic or carcinogenic action s usually are at least partially understood at a molecular level, wher eas antimutagenic and anticarcinogenic actions usually are not. It is possible there may be numerous specific mechanisms underlying the Janu s activity of different chemicals. (C) 1998 Elsevier Science B.V. All rights reserved.