Carcinogenic Activity of Alkylating Agents2

Inhibition of metabolic cooperation by cigarette smoke condensate and its fractions in V-79 Chinese hamster lung fibroblasts.

“…These findings correlate well with the previously published in vivo data of Wynder et al (4) and others (16,55,56), who detected tumor-promoting activity in components of CSC obtained in similar, but not identical, fractionation schemes. It is interesting to note that the benzene/petroleum ether eluate (which contains the polycyclic aromatic hydrocarbons) has high initiating activity and weak promoting activity.…”

“…Consistent with the two-stage theory of carcinogenesis, which evolved from the original observations by Rous and Kidd (9), Berenblum (10, 11), Mottram (12), and, later, Boutwell (13,14), it is evident that tobacco tars are complete carcinogens-containing both initiating and promoting elements. Such a conclusion is supported epidemiologically by the decreased lung cancer risk noted in persons who have stopped smoking (4, 15) (an observation consistent with the known reversibility of the tumor promotion phase of tumorigenesis) and experimentally by the presence of tumor promoters and cocarcinogens in tobacco tars and fractions demonstrated by using classical mouse skin painting assays (4,16 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

“…However, the much less studied procedures of co-carcinogenesis in which carcinogen and accessory substances are applied simultaneously over extended periods of time is a closer fit to the extended exposure of human smoking. Accordingly, 21 compounds were tested for co-carcinogenic activity, 18 of which are found in cigarette smoke condensate (Van Duuren and Goldschmidt, 1976;Van Duuren et al, 1973). Seven of the compounds were strong cocarcinogens that occur in cigarette smoke condensate (Van Duuren and Goldschmidt, 1976).…”

“…Although it was at first thought catechol might enhance the activity of enzymes that convert BP to a proximal carcinogen (Van Duuren et al, 1973), it was later found to actually inhibit the activity of the aryl hydroxylating enzymes (Van Duuren and Goldschmidt, 1976). The wide disparity of compounds that are cocarcinogens makes it highly unlikely that they have a common chemical mechanism.…”

“…In contrast, the content of promoters and co-carcinogens was sufficient to produce tumors in mouse skin that had either been initiated by a single dose of PAH (Gellhorn, 1958;Roe et al, 1959;Van Duuren et al, 1966) or by repeated simultaneous applications of weak doses of PAH with various constituents of the condensate (Van Duuren and Goldschmidt, 1976;Van Duuren et al, 1973). It was also noted that some PAHs that were themselves borderline or non-carcinogens could act as initiators when followed by promoters (Van Duuren et al, 1970).…”