Multiple Factors in Carcinogenesis*

Abstract

Because we in the study of carcinogenesis can get so involved in the multiple factorial nature, I would like to preface all the remarks which are to follow by a quote from Dr. Hueper 1 that I believe is appropriate in a discussion of OCCUpational cancer: ". , . there is no cancer without a carcinogen. . . ." t In this presentation I would like to comment first on the early recognition by investigators of the multiple factorial nature of carcinogenesis. Next, the component factors that relate to the host and the agent (or the actual exposure) will be treated. I will then present remarks concerning the significance of multiple factors in occupational cancer, and will close with comments on the broader ramifications of these significant points.Physicians of the early nineteenth century recognized that multiple factors influence the development of occupational cancer. With the exception of the chimney sweeps' cancer, which was reported in the eighteenth century,2 these were the first reports of occupational cancer. Early in the twentieth century, Alexander Scott, in 1923,3 described the skin lesions of the Scottish shale-oil workers. He revealed an appreciation of multiple factors when he said, "Accumulated evidence tends to show that some workmen have a greater tendency to be affected than others, the working conditions otherwise being the same."

Induction of micronuclei and sister chromatid exchanges by polycyclic and N‐heterocyclic aromatic hydrocarbons in cultured human lymphocytes

“…Many of these mixtures, such as coal tar, coal tar pitch, cigarette smoke, automobile exhaust, petroleum products, and coal gasification residues, contain polycyclic aromatic hydrocarbons (PAHs) and N-heterocyclic aromatic compounds (NHA), some of which are well-known experimental potent carcinogens [IARC, 1983;Warshawsky, 19921. It has been shown in animal studies that the carcinogenicity of coal-derived combustion mixtures in skin of PAHs other than BaP, heterocyclic analogs, and noncarcinogenic PAHs, as well as long-chain aliphatics, are factors that influence the carcinogenic potency of mixtures [Bingham et al, 1976;Niemeier et al, 1988;Bingham, 1988;Warshawsky et al, 19931. PAHs and NHAs have been of concern as potential human health hazards [IARC, 19831. PAHs and NHAs must first be metabolized to reactive metabolites that bind to DNA; they subsequently exert their mutagenic and/or carcinogenic effect in target tissue [Warshawsky, 1992;Miller, 1978;Hemminki, 1993;Gelboin, 19801.…”

Genotoxicity in water and sediment extracts from the St Lawrence river system, using the SOS chromotest

“…In fact, common hydrophBic biological degradation products, such as hydroxylamine, have been shown to be mutagenic and/or carcinogenic (Goodenough, 1978 (Berenbaum, 1985;Bingham et al, 1976).…”

The effects of a cocarcinogen, ferric oxide, on the metabolism of benzo[a]pyrene in the isolated perfused lung

“…Epidemiological and experimental evidence (Bingham et al, 1976) indicates that the interplay of multiple environmental factors appears to be responsible for the induction of lung cancer. It has been shown that the lungs are capable of metabolizing and binding foreign substances (Anderson and Eling, 1976;Cohen and Moore, 1976;Lubawy and Issac, 1980a,b;Niemeier and Bingham, 1972;Perera, 1981;Smith et al, 1978;Vainio et al, 1976;Warshawsky et al, 1980;Young, 1976).…”