Macromolecular Complexes Produced by Chemical Carcinogens and Ultraviolet Radiation

Summary

The effects of several carcinogenic and noncarcinogenic chemicals, ultraviolet light, and some presumably noncarcinogenic analogs of carcinogenic compounds were tested for their ability to induce in vitro complexes between purified nucleic acids and between nucleic acids and proteins. Several independent analytical methods were used to minimize the possibility of an unrecognized technical artifact. The results indicate that all of the ultimate tumor-producing agents tested thus far fall into two distinct groups with respect to their ability to form macromolecular complexes. Class A of these chemicals includes several mono- and polyfunctional alkylating agents. Both nucleic acid-nucleic acid and protein-nucleic acid adducts are produced in the presence of these compounds. Class B is exemplified by N-acetoxy-2-acetylaminofluorene, salts of beryllium, and ultraviolet light. Complexes between proteins and nucleic acids, although not between the nucleic acids themselves, are produced in the presence of Class B agents. Nonultimate carcinogenic chemicals such as N-hydroxy-2-acetylaminofluorene and 2-acetylaminofluorene do not give rise to any of these macromolecular complexes. However, they may be transformed into apparently active forms that then behave like Class B carcinogens after exposure to mouse or rat liver extracts (postmitochondrial supernatants). None of the macromolecular complexes were produced by noncarcinogenic chemicals. Along with our earlier observations, data reported in this paper indicate that a significant number and possibly all of the tumor-producing agents are able to form macromolecular complexes. We propose that, if such strong bonds between various chromosomal macromolecules are produced inside living cells exposed to carcinogenic agents, one extreme consequence of their formation may be a non-disjunction of daughter chromosomes during mitosis and/or a chromosomal breakdown. Such effects were often observed by other authors in tissues treated with carcinogens, and chromosomal aberrations are believed by some to correlate with malignant behavior.