Nitrogen mustards carcinogenicity

The lARC has classified nitrogen mustard HN-2 as probably carcinogenic to humans based on evidence that it causes leukemia in humans and cancers of the lung, liver, uterus, and large intestine in animals. ... 

HN-2 nitrogen mustard, administered mainly as the hydrochloride, has been tested for carcinogenicity in mice and rats by subcutaneous, intravenous, and intraperitoneal administration and by skin painting. It produced mainly lung tumors and lymphomas in mice after subcutaneous, intravenous, and intraperitoneal administration. Intravenous injection of nitrogen mustard to rats induced tumors in different organsk Application by skin... 

Bone marrow toxicity is the major side effect of chlorambucil. Nausea is uncommon or mUd, and hair loss does not occur. Chlorambucil shares the immunosuppressive, teratogenic, and carcinogenic properties of the nitrogen mustards. 

The three principal classes of cytotoxic agents used in the treatment of cancer all contain carcinogens, for example, Melphalen, a nitrogen mustard, adriamycin, an antitumor antibiotic, and methotrexate, an antimetabolite. Diethylstilbestrol (DES), a drug formerly widely used, has been associated with cancer of the cervix and vagina in the offspring of treated women. 

Animal carcinogen. Reasonably anticipated to be a human carcinogen and when used as a chemotherapeutic agent in combination with nitrogen mustard, a potent animal carcinogen, can result in acute nonlymphocytic leukemia.5 Adverse effects in 50-70% of... 

Studies of occupational exposures to sulfur mustard indicate an elevated risk of respiratory tract and skin tumors following long-term exposure to acutely toxic concentrations. Overall, several factors are important regarding the assessment of the carcinogenicity of sulfur mustard. Increased cancer incidence in humans appears to be associated only with exposures that caused severe acute effects, and occupational exposures tended to involve repeated exposures and repeated injury of the same tissues. Because the therapeutic use of the sulfur mustard analog nitrogen mustard is associated with an increased incidence of CML, the reports of CML in HD-exposed individuals appear to be relevant to the eareinogenicity of sulfur mustard. 

Mechlorethamine hydrochloride Nitrogen mustard topical antimitotic drug Carcinogen suppression of immunological defences Stevens-Johnson syndrome (SEDA-22, 172) (19)... 

Carcinogens can be divided into two general types those that act directly and those that act indirectly. Direct-acting carcinogens are those that interact with cellular constituents such as protein, lipids, and nucleic acids. There are relatively few direct-acting carcinogens (e.g., bis(chloromethyl)ether, ethylene oxide, and nitrogen mustard). 

Table 3.6 lists the long-term mustard complications affecting the respiratory tract, the eyes, the skin, the central nervous system and the bone marrow (8,25,26). As alkylating agents, sulfur and nitrogen mustards are carcinogens. 

By chemically reacting with nitrogen and oxygen atoms in DNA, these compounds can modify bases in DNA so as to distort the normal pattern of base pairing. If these modified nucleotides are not repaired, they allow an Incorrect nucleotide to be incorporated during replication. This type of carcinogen includes ethylmethane sulfonate (EMS), dimethyl sulfate (DMS), and nitrogen mustards. 

The incorporation of C from a X-labeled nitrogen mustard into purine fractions from the RNA and DNA of some mouse tissues was reported in 1957 by Wheeler and Skipper (58). Alkylation of liver RNA by the carcinogens dimethylnitrosamine and ethionine was reported by Farber and Magee in 1960 (59), with subsequent studies by others (reviewed in 1) demonstrating the incorporation... 

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