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Query: UMLS:C0596263 (
carcinogenesis
)
64,820
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The effect of dimethylarsenics on the pulmonary tumorigenesis initiated by 4-nitroquinoline 1-oxide (4NQO) in mice was examined. The exposure of mice to
dimethylarsinic acid
(
DMAA
), a major metabolite of inorganic arsenics in mammals, resulted in not only promotion but also progression of the tumorigenic process in the lungs of mice administered 4NQO. Furthermore, dimethylarsenics influenced the differentiation process in lung tumorigenesis by 4NQO. These results may pave the way for the elucidation of lung
carcinogenesis
caused by arsenics.
Carcinogenesis
1996 Apr
PMID:Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice. 862 89
Arsenicals are epidemiologically significant chemicals in relation to induction of urinary bladder cancer in man. In the present study, we investigated the dose-dependent promotion potential of
dimethylarsinic acid
(
DMA
), a major metabolite of inorganic arsenicals in mammals, for rat urinary bladder
carcinogenesis
. In experiment 1, 6-week-old male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then given one of several concentrations of
DMA
in their drinking water (groups 1-6: 0, 2, 10, 25, 50 and 100 p.p.m.) for 32 weeks. The development of preneoplastic lesions and tumors (papillomas and carcinomas) in the urinary bladder was enhanced by treatment with
DMA
in a dose-dependent manner. A significant increase in multiplicity of tumors (papillomas and carcinomas) was observed even at a low concentration of
DMA
(10 p.p.m.). On the other hand, no preneoplastic lesions and tumors were observed in the rats treated with
DMA
alone. In experiment 2, different concentrations of
DMA
(groups 1-4: 0, 10, 25 and 100 p.p.m.) in drinking water were administered to the rats for 8 weeks without prior initiation by BBN. A significant increase in the 5-bromo-2'-deoxyuridine labeling index and alteration of the surfaces of the urinary bladder epithelial cells, as revealed by scanning electron microscopy, provided evidence of a dose-dependent increase in cell proliferation due to the
DMA
treatment. These results suggest that
DMA
has the potential to promote rat urinary bladder
carcinogenesis
and one of the mechanisms involved is its stimulation of cell proliferation in the urinary bladder epithelium.
Carcinogenesis
1996 Nov
PMID:Promoting effects of dimethylarsinic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats. 896 60
Arsenic is a human carcinogen. On the other hand, selenium supplementation can inhibit induction of
carcinogenesis
by chemical carcinogens. The effect of selenium compounds on the cytotoxicity of
dimethylarsinic acid
(
DMA
) and on the induction of tetraploidy by
DMA
were studied using Chinese hamster V79 cells. Two selenium compounds were tested, sodium selenite and trimethylselenonium iodide (TMSeI). Trimethylselenonium is a major excretory product of selenite metabolism. The cytotoxicity of sodium selenite was 1000-fold greater than that of TMSeI. The cytotoxicity of
DMA
was about the same as that of TMSeI. The mitotic index for
DMA
administration was increased by these selenium compounds at low concentrations and decreased by them at high concentrations. The tetraploid index for
DMA
decreased with increasing concentrations of these selenium compounds. Tetraploidy is a form of aneuploidy, and aneuploidy is known to induce
carcinogenesis
. The finding that selenium inhibited induction of tetraploidy by
DMA
may yield clues to the role of selenium in the chemoprevention of
carcinogenesis
by chemical carcinogens.
...
PMID:The inhibitory effect of selenium on induction of tetraploidy by dimethylarsinic acid in Chinese hamster cells. 921 48
The modifying effects of
dimethylarsinic acid
(
DMA
), the major metabolite of ingested arsenicals in most mammals, on chemical carcinogenesis were investigated using rat in vivo models and reviewed here. In a multi-organ bioassay, rats pretreated with 5 carcinogens were administered
DMA
at various concentrations in their drinking water. Significantly increased tumor induction due to
DMA
was observed in the urinary bladder, kidney, liver, and thyroid gland. This was associated with significantly elevated ornithine decarboxylase activity in the kidneys of
DMA
-treated animals. To estimate the hazard levels of its promoting influence, further examinations were carried out concerned with urinary bladder and liver
carcinogenesis
. Doses of 25 and 50 ppm, respectively, of
DMA
were found capable of enhancing lesion development in the two organs. In conclusion, our data indicate that
DMA
is a carcinogen or promoter in the urinary bladder, liver, kidney and thyroid gland, in line with previous epidemiological findings.
...
PMID:Possible carcinogenic potential of dimethylarsinic acid as assessed in rat in vivo models: a review. 921 72
In a previous study, we found that sodium arsenite increased hepatic ornithine decarboxylase (ODC) activity and hepatic heme oxygenase (HO) activity, but did not cause any DNA damage in adult female rat liver or lung, suggesting that arsenite may be a promoter of
carcinogenesis
. In this study sodium arsenate, monomethylarsonic acid (MMA) and
dimethylarsinic acid
(
DMA
) were administered orally in equitoxic doses to adult female rats at 21 and 4 h prior to sacrifice. DNA damage (DD), cytochrome P450 content (P450), glutathione content (GSH), ODC, serum alanine aminotransferase (ALT) and HO were measured in liver and/or lung tissue. At 60 mg/kg in rat liver, sodium arsenate increased hepatic HO fivefold. MMA decreased ALT at 226 mg/kg, decreased ALT and GSH at 679 mg/kg and also increased P450 at 679 mg/kg in rat liver.
DMA
decreased ALT and hepatic GSH and increased hepatic HO at 387 mg/kg. In the lung,
DMA
decreased ODC at both 129 and 387 mg/kg. DD in lung tissue was significantly higher at 387 mg/kg
DMA
, demonstrating organ specific DNA damage. The biochemical effects and the inferred oncologic potential of the four major forms of arsenic (arsenate, arsenite, MMA and
DMA
) differ dramatically. The inorganic forms (arsenate and arsenite) are similar to each other (both good HO inducers); the methylated organic forms of arsenic (MMA and
DMA
) also share a similar pattern of biochemical effects (decreased GSH and ALT, increased P450). All six of the biochemical parameters studied were altered by
DMA
in either rat liver or lung.
...
PMID:Dimethylarsinic acid treatment alters six different rat biochemical parameters: relevance to arsenic carcinogenesis. 926 21
Arsenicals are epidemiologically significant chemicals in relation to induction of liver cancer in man. In the present study, we investigated the dose-dependent promotion potential of
dimethylarsinic acid
(
DMAA
), a major metabolite of inorganic arsenicals in mammals, in a rat liver
carcinogenesis
model. In experiment 1, glutathione-S-transferase placental form (GST-P)-positive foci, putative preneoplastic lesions, were employed as endpoints of a liver medium-term bioassay for carcinogens (Ito test). Starting 2 weeks after initiation with diethylnitrosamine, male F344 rats were treated with 0, 25, 50 or 100 ppm of
DMAA
in the drinking water for 6 weeks. All animals underwent two-thirds partial hepatectomy at week 3 after initiation. Examination of liver sections after termination at 8 weeks revealed dose-dependent increases in the numbers and areas of GST-P-positive foci in
DMAA
-treated rats as compared with controls. In experiment 2, ornithine decarboxylase activity, which is a biomarker of cell proliferation, was found to be significantly increased in the livers of rats treated with
DMAA
. In experiment 3, formation of 8-hydroxydeoxyguanosine, which is a marker of oxygen radical-mediated DNA damage, was significantly increased after administration of
DMAA
. These results indicate that
DMAA
has the potential to promote rat liver
carcinogenesis
, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.
...
PMID:Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver. 947 32
We demonstrate in this study the cytotoxic effects of inorganic arsenicals, arsenite and arsenate, and organic arsenic compounds, monomethylarsonic acid (MAA),
dimethylarsinic acid
(
DMAA
), and trimethylarsine oxide (TMAO), which are metabolites of inorganic arsenicals in human bodies, using murine macrophages in vitro. Inorganic arsenicals, both arsenite and arsenate, are strongly toxic to macrophages, and the concentration that decreased the number of surviving cells to 50% of that in untreated controls (IC50) was 5 or 500 microM, respectively. These inorganic arsenicals mainly caused necrotic cell death with partially apoptotic cell death; about 80% of dead cells were necrotic, and 20% were apoptotic. The inorganic arsenicals also induced marked release of an inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), at cytotoxic doses. This strong cytotoxicity of an inorganic arsenical, arsenite, might be mediated via active oxygen and protease activation because it was inhibited by the addition of some antioxidant reagents, such as superoxide dismutase (SOD), catalase, and GSH, or by a peptide inhibitor of interleukin-1 beta-converting enzyme (ICE). It is likely that these immunotoxic effects of inorganic arsenicals may evoke both immunosuppression and inflammation, and they may be central factors causing
carcinogenesis
and severe inflammatory responses, such as hepatomegaly and splenomegaly, in chronic arsenicosis patients who daily ingested arsenic-contaminated well water. In contrast, the cytotoxic effects of methylated arsenic compounds were lower than those of inorganic arsenicals. The IC50 value of
DMAA
was about 5 mM, and MAA and TMAO had no toxicity even at concentrations over 10 mM. Additionally, these methylated chemicals suppressed the TNFalpha release from macrophages.
DMAA
induced mainly apoptotic cell death in macrophages as indicated by cellular morphological changes, condensed nuclei, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and DNA fragmentation. However, the cytotoxicity of
DMAA
might be induced via a different mechanism from that of inorganic arsenicals because it was not abolished by the additions of SOD, catalase, or ICE inhibitor. Conversely, GSH enhanced the toxicity of
DMAA
. These data suggest that methylation of inorganic arsenicals in mammals plays an important role in suppression of both severe immunosuppression and inflammatory responses caused by inorganic arsenicals.
...
PMID:Inorganic and methylated arsenic compounds induce cell death in murine macrophages via different mechanisms. 954 97
The pulmonary tumorigenicity of
dimethylarsinic acid
(
DMAA
), a main metabolite of inorganic arsenics, was examined in A/J mice fed with drinking water containing
DMAA
for 25 and 50 weeks. Mice fed with 400 ppm
DMAA
for 50 weeks produced more pulmonary tumors than untreated mice (mean number per animal 1.36 versus 0.50; P < 0.05). Histological examination revealed that the number of mice which bore adenocarcinomas or papillary adenomas correlated with the concentration of
DMAA
given (untreated versus 400 ppm; P = 0.002), suggesting that
DMAA
could promote tumorigenic processes. These results are consistent with the epidemiological studies on the pulmonary
carcinogenesis
of arsenics and suggest that
DMAA
alone can act as a carcinogen in mice.
...
PMID:Dimethylarsinic acid, a main metabolite of inorganic arsenics, has tumorigenicity and progression effects in the pulmonary tumors of A/J mice. 956
The present study was conducted to determine the carcinogenicity of
dimethylarsinic acid
(
DMA
) administered to male F344 rats in a 2 year bioassay. A total of 144 rats (10 weeks old at the start) were divided into four groups of 36 rats each. Groups 1-4 received
DMA
(purity 100%) at concentrations of 200, 50, 12.5 and 0 p.p.m. in the drinking water, respectively, for 104 weeks. From weeks 97 to 104, urinary bladder tumors were observed in 12 of 31, eight of 31 and none of 33 in groups 1-3, respectively. No bladder tumors were observed in group 4. The present study demonstrated that long-term p. o. administration of
DMA
induced urinary bladder carcinomas in male F344 rats. Therefore, the results indicate that
DMA
is carcinogenic for the rat urinary bladder, which may be related to the human carcinogenicity of arsenicals.
Carcinogenesis
1999 Sep
PMID:Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats. 1046 37
The effect of
dimethylarsinic acid
(
DMA
) on skin tumorigenesis by UVB irradiation was examined. Hairless mice (Hos: HR-1) irradiated with UVB at a dose of 2 kJ/m(2) twice weekly, were fed with drinking water containing 1000 ppm
DMA
, a main metabolite of inorganic arsenics, produced more skin tumors than
DMA
-untreated mice. Histopathological examination revealed that the mouse malignant tumors with severe atypism appeared only in the treatment group of UVB plus 1000 ppm
DMA
. These positive results point out the importance of dimethylated metabolites of inorganic arsenic in the process of skin
carcinogenesis
.
...
PMID:The role of orally administered dimethylarsinic acid, a main metabolite of inorganic arsenics, in the promotion and progression of UVB-induced skin tumorigenesis in hairless mice. 1075 9
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