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Structure-Activity Relationships Among The Carcinogenic Aromatic Amines
Pages 60-85

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From page 60... ... discussed species and tissue differences in aromatic amine metabolism as one factor in determining the distribution of induced tumors. Other factors, such as differing tissue and species levels in prereplicative DNA repair, cell proliferation, and hormonal responsiveness, also need to be considered before a comprehensive picture of tumor distribution can be formulated. Read the entire page →
From page 61... ... represent some of the more potent carcinogens. Another important discovery has been the demonstration of the cons iderable carcinogen ic potency of certa in amino and nitroheterocyclic aromatics, such as the derivatives of S-nitrofuran, nitrothiazole, and nitroimidazole . Read the entire page →
From page 62... ... Painting ~-aminoszobenzene or a range of similar chemicals on rat skin leads to skin tumors (Fare and Orr, 1965; Fare, 19661. There is very limited evidence for the importance of an alkyl group on the nitrogen to the carcinogenic potency of aromatic amines. Read the entire page →
From page 63... ... Honoalkylaromatic dines can be converted to the corresponding n$trosaeines in the presence of nitrous acid at an acid pE. Arylation Ablation of the amino group to diarylamines or triarylamines is believed to abolish carcinogenic activity, although the evidence for this conclusion is tenuous. Read the entire page →
From page 64... ... Aroyl Der ivatives Aroyl derivatives bave been examined, particularly in the 2-fluorenylamine ser ies . Although N-2-fluorenylbenzamide is inactive, the corresponding N-hydroxy-2-fluorenylbenzamide is carcinogenic. Read the entire page →
From page 65... ... . Azo Compounds and Bydrazo Compounds m eve compounds are reduced in the anaerobic portions of the gastrointestinal tract, or by the tissue enzyme, azoreductese, to compounds, each of which contains an amino group. Read the entire page →
From page 66... ... Me high carcinogenic potency of ~ series of dyes (Direct Black 38, Direct Brown 95, and Direct Blue 6) , which are capable of reduction to benzidine, has been reported by the National Cancer Institute (1978~. Read the entire page →
From page 67... ... The heterocyclic chemicals are d~wuseed separately later in this chapter. Ring substituents on the carcinogenic potential of aromatic amines are subd ivided into Analogs of ~-dimethylaminoszobenzene Aromatic amines with single amino groups Analogs of the phenylenediamines Analogs of benzidine. Read the entire page →
From page 68... ... Table 3-1 Effect of Substituents on the CarcinogenicaAct~ivity of N,N-DimethYl-p-phenyl2aoanilineSubstitilPot 2 3 2' a' 4' 2,3' 2,4' 2,6' 3',4' 3''5' 2 "4'. -CH3 -C2H5 -CF3 -F -C1 -Br -OH -OCH3 -oC2Hs - NO2 -NH2 -SO3H -CO2H + + + ~ ~ + + ~ + + + + ~ + _ + + + a From Clayson and Garner, 1976, with permission. Read the entire page →
From page 69... ... ~s1 In Icy � o Q Read the entire page →
From page 70... ... , may be deactivating (National Cancer Institute, in press) Read the entire page →
From page 71... ... for carcinogenicity (National Cancer Institute, 1978a,b,c,d,e,f; 1979a,b; Weisburger et al., 19781. A limited number of these agents are effective carcinogens, including 2, 4-diaminotoluene, 5-nitro~o-anisidine, and 4-chloro~o-phenylenediamine; others, under the test conditions used, exhibited more marginal carcinogenicity, including 2-N-~-phenylenediamine, 2,5-diaminotoluene sulfate, 2,4-dinitrotoluene, and tetrafluorometaphenylenediamine. Read the entire page →
From page 72... ... , in which o-methyI- or o-chloro-substitution appears to enhance carcinogenicity (Munn, 1967~. NTTRO- AND AMTNO-AROMATIC ""R=YCLIC =~=DS In the furan, thiophene, imidazole, and thiazole series, both of the unsaturated bonds provide a pair of ~ electrons, and one of the betero atoms provides a lone pair of electrons to form the aromatic sextet. Read the entire page →
From page 73... ... Structure-activity relationships are cliff icult to evaluate because of the competing effects of the betero atoms, the substitutents, and the various conjugated aromatic systems. It does, however, appear that compounds with two conjugated aromatic ring systems are, when carcinogenic, more potent than are single-ring systems. Read the entire page →
From page 74... ... 3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1_ 1 1 1 1 1 1 1 1 1 1 + ~re I + I I I I 1 1_ 1 1 I I I I I I I L 1 + 1 1~1 1 1 1 ++++ I I I I I I I I t I I I 0 ~.e 0 0 ~ 0 ~ ~.e 0 e 310 11e 11t ~ 1 1 i] oo ooooo ooo 0 0 o 1_ 1 1 1 1 1 1 1 1 I I I I l I I 1 1 1 +1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ~ t I 1 1 1 1 1 1 1 1 ++ _ 1 1 + +_ 1 1 1 1 ~ 1 1 t I 1 1 ~ I I ~ 81 Ill, eae I 1 1 1 1 1 1 1 1 ++ 1 1 1 ~ _ 1 1 1 1 1 1 ~ 1 1 1 1 1 1 1 1 1 1 eae I I I 1 I ~ 74 Read the entire page →
From page 75... ... Ear example, the methemoglobinemis induced by aniline may stress the spleen, which removes deter is in red blood cells from the circulation, thereby setting up tbe conditions for splenic tumorigenesis. ~C~loroaniline induces similar cancers and, likewise, induce'; high levels of methemoglobinemia (National Cancer Institute, 1979d) Read the entire page →
From page 76... ... 2,4-Diaminotoluene (National Cancer Institute, 1978h) induced hepatocellular carcinomas in male and female rats and in female mice. Read the entire page →
From page 77... ... 1978 . Carc inogenes is -- A Comprehens ive Surrey, Vol. Read the entire page →
From page 78... ... 1967. The conversion of noncarcinogenic aromatic amides to carcinogenic arylhydroxamic acids by synthetic N-hydroxylation. Read the entire page →
From page 79... ... American Chemical Society, Wash ington, D Read the entire page →
From page 80... ... Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, Md. Read the entire page →
From page 81... ... Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, Md. Read the entire page →
From page 82... ... Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, Md. Read the entire page →
From page 83... ... Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, Md. Read the entire page →
From page 84... ... U.S Public Health Service, National Institutes of Health, Washington, D.C. Read the entire page →
From page 85... ... 1978. Testing of twenty-one environmental aromatic amines or der ivatives for long-term toxicity for carcinogenicity. Read the entire page →

From page 60...

... discussed species and tissue differences in aromatic amine metabolism as one factor in determining the distribution of induced tumors. Other factors, such as differing tissue and species levels in prereplicative DNA repair, cell proliferation, and hormonal responsiveness, also need to be considered before a comprehensive picture of tumor distribution can be formulated.

Structure-Activity Relationships Among The Carcinogenic Aromatic Amines Pages 60-85

Structure-Activity Relationships Among The Carcinogenic Aromatic Amines
Pages 60-85