Procarcinogenic species

CYP1A2. CYP1A2 has been implicated in the activation of procarcinogenic species such as aflatoxin Bl, 2-acetylaminofluorene, and other arylamines. It tends to favor aromatic substrates, both heterocyclic aromatic substrates like caffeine and aromatic substrates like phenacetin (10). In the case of caffeine, 1A2 is the major isoform catalyzing the... 

Nitrogen species, such as nitrate and nitrite, are known to be confirmed procarcinogens. The excessive input of these nitrogen compounds with food and drinking water in the presence of tertiary amines, for instance, from medicines, can lead to the formation of carcinogenic N-nitrosoamines. 

CYP1. The CYP1A subfamily contains two members, CYP1A1 and CYP1A2, which are involved in drug metabolism and have sparked considerable interest because they also seem to be associated with the metabolic activation of procarcinogens to mutagenic species. 

Rodriguez-Arnaiz, R., Vogel, E.W. Szakmary, A. (1993) Strong intra-species variability in the metabolic conversion of six procarcinogens to somatic cell recombinagens in Drosophila. Mutagenesis, 8, 543-551... 

Formation of a dihydrodiol by hydration of epoxide groups can be an important detoxication process in that the product is often much less reactive to potential receptors than is the epoxide. However, this is not invariably the case because some dihydrodiols may undergo further epoxidation to form even more reactive metabolites. As shown in Figure 7.3, this can happen with benzo(a)pyrene 7,8-epoxide, which becomes oxidized to carcinogenic benzo(a)pyrene 7,8-diol-9,10-epoxide. The parent polycyclic aromatic hydrocarbon benzo(a)pyrene is classified as a procarcinogen, or precarcinogen, in that metabolic action is required to convert it to a species, in this case benzo(a)pyrene 7,8-diol-9,10-epoxide, which is carcinogenic as such. 

These short-lived species, in turn, promote the propagation of chain peroxidation of membrane lipids, thus disrupting the cellular integrity, or they may oxidize also various xenobiotics that are in the vicinity. Indeed, the hydroperoxide dependent oxidation process has been implicated as one of the mechanisms of conversion of procarcinogens to carcinogens (6,9) ... 

Figure 15. As shown here with DMAB, conjugates nay serve as procarcinogens whose sites of carcinogenicity differ among species because of dissimilar routes of transport and excretion.

Secondary or procarcinogens, which themselves are inert, must first be activated to ultimate carcinogens by host-mediated enzymatic reactions. The host-mediated activation can be by species-specific enzymes. This explained the previously puzzling observations of certain chemicals being carcinogenic in some species and not in others. 

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