Carcinogenic Nitroso Compounds

Magee, Peter; Barnes, J. M.

doi:10.1016/s0065-230x(08)60079-2

Cited by 1,009 publications

(231 citation statements)

References 216 publications

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“…The yields of tumours at the 48h and 60h intervals are not increased significantly. (Magee and Barnes, 1967). This paper defines potencies for liver and kidneys in the local mouse strain, and supports the view that DEN is more potent for the liver and DMN for the kidney with the dose and conditions of these particular experiments.…”

Section: Kidney Lesionssupporting

confidence: 71%

Influence of carbon tetrachloride on induction of tumours of the liver and kidneys in mice by netrosamines

Pound¹

1978

Br J Cancer

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Summary.-Mice were given a single dose of nitrosodimethylamine, nitrosodiethylamine or nitrosomethylethylamine and the yield of tumours and related lesions in the livers determined 12 months later. A hepatonecrotic dose of CC14 24 or 48 h before the nitrosamines, increased the yields of hepatocellular tumours and proliferative foci in the livers, whereas when given 60 h before the nitrosamines there was no significant effect.

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Section: Kidney Lesionssupporting

confidence: 71%

Influence of carbon tetrachloride on induction of tumours of the liver and kidneys in mice by netrosamines

Pound¹

1978

Br J Cancer

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“…The chemical mechanisms of carcinogenesis by these nitrosamines in humans are therefore of considerable interest. 3,4 Numerous studies have shown that several cytochrome P450 (CYP) enzymes, particularly cytochrome P4502A6 (CYP2A6) and cytochrome P4502E1 (CYP2E1), catalyze metabolic activation of nitrosamine derivatives, including N-nitroso-dialkyiamines and tobacco-smoke-related nitrosamine. [5][6][7][8] Genetic polymorphisms for CYP2A6 have been described and 2 variant alleles associated with reduced activity have been identified.…”

mentioning

confidence: 99%

Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Tsukino

Kuroda

Qiu

et al. 2002

Intl Journal of Cancer

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Cytochrome P450 (CYP) 2A6 and CYP2E1 are enzymes with a high ability to activate a nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to its potent and ultimate carcinogens. The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies. In our study, 120 Japanese patients with gastric adenocarcinoma and 158 healthy controls were compared for frequencies of CYP2A6 and CYP2E1 genotypes. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion allele, which causes lack of the enzyme activity, was significantly higher in the gastric cancer patients than in the healthy control subjects (OR ‫؍‬ 3.14, 95% confidence interval (95% CI) ‫؍‬ 1.05-9.41). Subdividing gastric adenocarcinoma according to tumor differentiation, patients with the well-differentiated type were 4. Although gastric cancer incidence has fallen markedly over the past 50 years in industrialized nations, it remains the second leading cause of cancer death in Japan. Epidemiological and experimental evidence have indicated that excess salt intake, which promotes cell replication, increases gastric cancer risk. 1,2 There is considerable evidence to support the view that carcinogenic N-nitrosamine derivatives are important factors in human cancer, including gastric cancer. The chemical mechanisms of carcinogenesis by these nitrosamines in humans are therefore of considerable interest. 3,4 Numerous studies have shown that several cytochrome P450 (CYP) enzymes, particularly cytochrome P4502A6 (CYP2A6) and cytochrome P4502E1 (CYP2E1), catalyze metabolic activation of nitrosamine derivatives, including N-nitroso-dialkyiamines and tobacco-smoke-related nitrosamine. [5][6][7][8] Genetic polymorphisms for CYP2A6 have been described and 2 variant alleles associated with reduced activity have been identified. Variant 1 (CYP2A6*2) and Variant 2 (CYP2A6*3) are the results of amino acid exchanged for wildtype (CYP2A6*1). Recently, Kitagawa et al. 9 revealed that a novel deletion genotype variant of the CYP2A6 gene was one of the major polymorphic genes in Japanese lacking CYP2A6 activity.In addition, CYP2E1 represents a major CYP isoform in the human liver and is also expressed in extrahepatic tissue. This enzyme can be induced by certain chemicals, such as ethanol and large interindividual variations have been observed, suggesting that the variation may be due to genetic polymorphism. It was reported that RsaI polymorphism, which is located in the 5Ј-flanking region of CYP2E1 gene, has been shown to be associated with the transcriptional regulation of gene expression, resulting in different expression levels of the CYP2E1 mRNA. 6 CYP2E1 participated in the metabolic activation of various N-nitrosamines, including a potent tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. 8,10 Several recent reports have investigated the role of CYP2A6 genetic polymorphisms in tobacco dependence and lung cancer risk, with conflicting results. [11][12][13][14][15] Less ...

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“…This cou. ]d be re]a~ed w~th oxidation--ied,uc£~on of glulathSone w,h]ch ~s probably a steadysta~e dependent, ira par~, on glnta~one zeductas~ and glutathione perox~dase activities ~2-4].The present communication compares the activities of these enzymes in rat hepatomous ]h, er, 5nduced by diethy!nitros~.mine [5], with control ra~ liver and show~ that GSSG reductase ]s increased and GSH peioxi,dase ~ decreased iv the l~er of ram treated with dieflay]nJtrosamine. 5"he e£feet is sex independent.…”

mentioning

confidence: 89%

Glutathione reductase and glutathione peroxidase activities in hepatomous livers of rats treated with diethylnitrosamine

Pinto

Barley

1973

FEBS Letters

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An increased concentration of acid-soluble thiols appear ?:o be involved ha ce~ div:mio~ and ha turnout formation {1 ]. This cou.]d be re]a~ed w~th oxidation--ied,uc£~on of glulathSone w,h]ch ~s probably a steadysta~e dependent, ira par~, on glnta~one zeductas~ and glutathione perox~dase activities ~2-4].The present communication compares the activities of these enzymes in rat hepatomous ]h, er, 5nduced by diethy!nitros~.mine [5], with control ra~ liver and show~ that GSSG reductase ]s increased and GSH peioxi,dase ~ decreased iv the l~er of ram treated with dieflay]nJtrosamine. 5"he e£feet is sex independent. Materials and methods J. MaterialsAll the chemicals used w :re of the purest grade available. GSH, GSSG, NADPH and yeast glntaflfione reductase were obtained from C.F. Boehfinger and Soehne GmbH, Mann:heim, Germany. All the other reagents u~ed were supF]~ed by British Drug Houses, L~d., Poole, Dorset, ,Great Britain. Animals and diemWistar rats were from the Sheffield University Anianal House colony and were fed ad lib~um with Ox~od die~ 86 (Herbert C. Style~ Ltd., Bew dley, Worts.). Dielh)qnitzosffrai~e indue;ion of hver turnoutswa~ carried out adding die~y]ni*rozam :no to ~he dfin~ng wate~ (50 rng/!~) of 20 rats (l 0 males and 10 females) for about 4 months. After th :; t~ne ~e animals started dy'mg and for this reason the remaining treated rats and the control rats were killed at once for the exp~.r:..arutal measurements. The l_vers were removed an~ after pleparation of microscopic section for ]bght microscopy they were kept in the deep freeze. In/he Ik, ers of the rats treated va~ diethy]niires ,amine there were large amounts of aaedp~a~t~c fo=i and a few areas of necroMs w)fich were absent in V.he controls. The average w~aght of the control rats was 390 -+ 25 g for males and 252 +-% 23 g for females and that of the treated rats was 2~0 4---30 g and 1~;0 ---17 g, respecdwely. Thus the treated rats were on average about 70% of the weight of control ra~. Male rats weighing

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Carcinogenic Nitroso Compounds

Cited by 1,009 publications

References 216 publications

Influence of carbon tetrachloride on induction of tumours of the liver and kidneys in mice by netrosamines

Influence of carbon tetrachloride on induction of tumours of the liver and kidneys in mice by netrosamines

Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Glutathione reductase and glutathione peroxidase activities in hepatomous livers of rats treated with diethylnitrosamine

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