Carcinogens direct-acting

Some laboratory studies with rats and mice have linked trichloroethylene exposure to various types of cancers. Several of these studies, however, should be viewed cautiously, since the tumorigenic activity might be influenced by the presence of direct-acting compounds, namely the epoxides (e.g., epichlorohydrin) added as stabilizers in trichloroethylene. Epoxides are known to be very reactive, and some, such as epichlorohydrin, are potent carcinogens themselves. 

The above scheme satisfies much of the metabolic data however, some of it is speculative, and it is certainly incomplete. The evidence for the formation of the a-hydroxylated intermediate is circumstantial. The acetate ester of a-hydroxylated dimethylnitrosamine has been prepared (12.13) and has been found to be a potent, directly acting carcinogen (14). Other esters of a variety of a-hydroxylated nitros-amines have also been prepared (15). While it has been shown that DMN acetate is hydrolyzed to hydroxymethylmethyl-nitrosamine by an esterase enzyme, it has been pointed out that these derivatives of the a-hydroxylated nitrosamines also dissociate to N-nitrosoimmonium ions (15 16). 

These nltrosated amides, In contrast to the nltrosamlnes, do not require metabolic activation in order to alkylate cellular nucleophilic targets. Thus, many of these substances are directly acting mutagens and also carcinogens (38. ... 

Dimethyl carbamoyl chloride is a direct-acting alkylating agent with a wide spectrum of genotoxic activity." ACGIH has classified dimethyl carbamoyl as A2-a suspected human carcinogen with no threshold limit value (TLV). 

Toxicology. Epichlorohydrin is a severe irritant of skin, eye, and respiratory tract. Repeated or prolonged exposure can cause lung liver and kidney damage. It is a direct-acting mutagen and is carcinogenic in experimental animals. 

BPL is a direct-acting alkylating agent and forms DNA adducts. It is mutagenic in a wide variety of in vitro and in vivo systems, both in somatic and germ cells. The lARC has determined that BPL is carcinogenic in experimental animals and that it is possibly carcinogenic to humans. ... 

Initially, major attention was focused on emissions of diesel soot from light- and heavy-duty motor vehicles, because the particle extracts contained such direct-acting bacterial mutagens and animal and possible human carcinogens (IARC Group 2B, 1989) as 1-nitropyrene (1-N02-PY) and the 1,6- and 1,8-dinitropyrenes (DNP), as well as a third isomer, 1,3-dinitropyrene, IARC Group III. For example, Paputa-Peck and coworkers (Paputa-Peck et al., 1983 IARC, 1989) reported 100 nitro-PAHs (17 positively identified) in... 

As discussed in detail in Section 5, with chemical carcinogens, the route of exposure can be an important determinant of the site of cancer induction, particularly with direct-acting carcinogens which may act at the initial point of contact. For the majority of carcinogens, however, which require metabolic activation, the location in the body of activating enzymes is thought to be the major determinant of the site of carcinogenesis. 

Roldan-Arjona, T., Luque-Romero, F.L., Ruiz-Rubio, M. Pueyo, C. (1990) Quantitative relationship between mutagenic potency in the Ara test of Salmonella typhimurium and carcinogenic potency in rodents. A study of 11 direct-acting monofunctional alkylating agents. Carcinogenesis, 11, 975-980... 

BULL You re really referring to direct-acting carcinogenic compounds for the most part, the unstable or reactive electrophilic compounds. 

The inhibitory effect of sitosterol (33) on colon tumor formation in rats treated with the carcinogen A-methyl-A-nitrosourea (MNU) has been studied, and it has been demonstrated that compound 33 nullified in part the effect of this direct-acting carcinogen on the colon [44]. This suggested that phytosterols may have a protective dietary action to retard colon tumor formation. 

Therefore, when it became clearly understood that atrazine is neither estrogenic nor a genotoxic, direct-acting carcinogen - and that the atrazine-associated tumor responses appeared only in female SD rats, a strain with a high, normally occurring incidence of mammary tumors - it became important to study the effect of high doses of atrazine on the SD animal model s own endocrine system and hormonal milieu. 

Direct-acting carcinogens 5. Require metabolic activation... 

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