Cellular injury and carcinogenesis. Inhibition of metabolism of dimethylnitrosamine by aminoacetonitrile

Fiume, L.; Campadelli-Fiume, Gabriella; Magee, Peter; Holsman, J. W.

doi:10.1042/bj1200601

Cited by 52 publications

(5 citation statements)

References 23 publications

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“…The toxic effects were reduced in animals given a protein-free diet (McLean and Verschuuren, 1969) or treated by other means that reduced the formation of microsomal enzymes concerned in the metabolism of DMN (Venkatesan, Arcos and Argus, 1968;Venkatesan, Argus and Arcos, 1970;Fiume et al, 1970;Schmahl et al, 1971;Magour and Nievel, 1971;Swann and McLean, 1971;Mirvish and Sidransky, 1971;Somogyi et al, 1972;Pound, Horn and Lawson, 1973). On the other hand, a protein-free diet increased the susceptibility of animals to the carcinogenic action of DMN for the kidneys but not apparently for the liver (McLean and .…”

mentioning

confidence: 99%

Increased Carcinogenic Action of Dimethylnitrosamine after Prior Administration of Carbon Tetrachloride

Pound¹,

Lawson²,

Horn³

1973

Br J Cancer

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Summary.-Rats were given a single dose of dimethylnitrosamine (DMN, 20 mg/kg body weight) alone or 42 or 60 hours after a non-lethal hepatotoxic dose of carbon tetrachloride (CC14) and killed 12 months later. DMN alone produced no tumours in the kidney and a few in the liver, but when given 42 hours after CC14, tumours formed in the kidneys and the number in the liver was increased. When given after 60 hours, the incidence of kidney tumours was less but that of liver tumours was further increased. A larger dose of DMN (40 mg/kg) was tolerated 42 hours after CC14 and enhanced the number of kidney and liver tumours, the latter apparently due to an increased proportion of cholangiomata. Numerous small focal proliferations of atypical liver cells and of bile duct epithelium were observed after treatment with DMN. The incidence of these lesions in the different experimental treatments varied in a similar manner to the liver tumours.

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mentioning

confidence: 99%

Increased Carcinogenic Action of Dimethylnitrosamine after Prior Administration of Carbon Tetrachloride

Pound¹,

Lawson²,

Horn³

1973

Br J Cancer

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“…5 and 6) corresponds to the reported inhibitory effects of AAN on DMNA breakdown in rats and its resulting toxic and lethal manifestations (14)(15)(16)(17)(18). The depressed DMNA mutation frequency seen at AAN levels of 20.0 and 100.0 mg/kg, indicates a greatly decreased formation (or release) of active mutagens to the indicator cells in the peritoneal cavity.…”

Section: Discussionmentioning

confidence: 99%

“…One hour after the bacterial injection, the mice were injected "intramuscularly (IM) with DMNA (20.0 mg/kg), NM (100.0 mg/ kg), or NMU (10.0 mg/kg) in saline. The mice were then sacrificed at intervals of 5,10,15,20,30,60, and 120 min following mutagen injection, and the bacteriological procedures were performed as previously described (7). The spontaneous reversion frequency was determined at 120 min.…”

Section: Introductionmentioning

confidence: 99%

The evaluation of chemical mutagenicity data in relation to population risk: some factors affecting the host-mediated assay response.

Zeiger¹

1973

Environ Health Perspect

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“…All of the radioactivity was displaced by this and trapped in the alkali. The alkaline solution was then treated with BaC12 and the precipitated Ba'4C03 washed and counted for radioactivity as described by Fiume et al (1970). All of the volatile radioactivity present from the enzyme assay could be accounted for as Ba'4C03.…”

Section: S-adenosyl[carboxyl-14c]methioninementioning

confidence: 99%

The decarboxylation of S-adenosylmethionine by detergent-treated extracts of rat liver

Wilson

Corti

Hawkins

et al. 1979

Biochemical Journal

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1. The production of (14)CO(2) from S-adenosyl[carboxyl-(14)C]methionine by rat liver extracts was investigated. It was found that, in addition to the well-known cytosolic putrescine-activated S-adenosylmethionine decarboxylase, an activity carrying out the production of (14)CO(2) could be extracted from a latent, particulate or membrane-bound form by treatment with buffer containing 1% (v/v) Triton X-100 [confirming the report of Sturman (1976) Biochim. Biophys. Acta428, 56-69]. 2. The formation of (14)CO(2) by such detergent-solubilized extracts differed from that by cytosolic S-adenosylmethionine decarboxylase in a number of ways. The reaction by the solubilized extracts did not require putrescine and was not directly proportional to time of incubation or the amount of protein added. Instead, activity a showed a distinct lag period and was much greater when high concentrations of the extracts were used. The cytosolic S-adenosylmethionine decarboxylase was activated by putrescine, showed strict proportionality to protein added and the reaction proceeded at a constant rate. Cytosolic activity was not inhibited by homoserine or by S-adenosylhomocysteine, whereas the Triton-solubilized activity was strongly inhibited. 3. By using an acetone precipitate of Triton-treated homogenates as a source of the activity, it was found that decarboxylated S-adenosylmethionine was not present among the products of the reaction, although 5'-methylthioadenosine and 5-methylthioribose were found. Such extracts were able to produce (14)CO(2) when incubated with [U-(14)C]-homoserine, and (14)CO(2) production was greater when S-adenosyl[carboxyl-(14)C]methionine that had been degraded by heating at pH6 at 100 degrees C for 30min (a procedure known to produce mainly 5'-methylthioadenosine and homoserine lactone) was used as a substrate than when S-adenosyl[carboxyl-(14)C]methionine was used. 4. These results indicate that the Triton-solubilized activity is not a real S-adenosylmethionine decarboxylase, but that (14)CO(2) is produced via a series of reactions involving degradation of the S-adenosyl-[carboxyl-(14)C]methionine. It is probable that this degradation can occur via several pathways. Our results would suggest that part of the reaction occurs via the production of S-adenosylhomocysteine, which can then be converted into 2-oxobutyrate via the transsulphuration pathway, and that part occurs via the production of homoserine by an enzyme converting S-adenosylmethionine into 5'-methylthioadenosine and homoserine lactone.

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Cellular injury and carcinogenesis. Inhibition of metabolism of dimethylnitrosamine by aminoacetonitrile

Cited by 52 publications

References 23 publications

Increased Carcinogenic Action of Dimethylnitrosamine after Prior Administration of Carbon Tetrachloride

Increased Carcinogenic Action of Dimethylnitrosamine after Prior Administration of Carbon Tetrachloride

The evaluation of chemical mutagenicity data in relation to population risk: some factors affecting the host-mediated assay response.

The decarboxylation of S-adenosylmethionine by detergent-treated extracts of rat liver

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