Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cocarcinogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1986

Neoplastic transformation in the planarian: I. Cocarcinogenesis and histopathology.

Although several investigators have reported that exposure to mammalian carcinogens induces abnormal tumorlike growths and teratogenic remodeling in planarians, there is no general agreement that these, or comparable responses in any other invertebrates, model mammalian carcinogenesis. To investigate this question, freshwater planarians of the species Dugesia dorotocephala were exposed to culture water containing an initiator and a promoter, either alone or in combination. Cadmium, a potent carcinogen, was used as an initiator in the protocol. Treatment with sublethal concentrations of cadmium sulfate produced a benign, but persistent, tumor in a small percentage of the planarians. The addition of 12-O-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester and well-known promoter, to the cadmium-containing solutions resulted in the induction of a progressive, potentially lethal, transplantable tumor in a large proportion of the treated flatworms. Light and electron microscopy revealed this particular tumor to be composed both of immature cells and of a single mature cell type: newly differentiated, but transformed, reticular cells. Further examination of the infiltrating tissue formations elucidated the profile of differentiation, from a population of mitotically active transformed stem cells through the transitional stages in the associated reticuloma. These results suggest that 1) the freshwater planarian displays the major phenomenology of mammalian cocarcinogenesis and that 2) the planarian reticuloma models several important features of a neoplastic stem cell disease.

Animals↗
PubMed1996

Biomarkers of effect in evaluating metalaxyl cocarcinogenesis. Selective induction of murine CYP 3A isoform.

The ability of metalaxyl, whose mutagenic/cocarcinogenic activity has as yet not been clarified, to affect specific biomarkers related to non-genotoxic cocarcinogenesis, was investigated. Several CYP-dependent reactions have been studied in liver, kidney and lung microsomes derived from male and female Swiss Albino CD1 mice treated i.p. with single (200 or 400 mg/kg b.w.) or repeated (200 mg/kg b.w., 3 days) administrations of fungicide. No significant changes in both absolute and relative liver, kidney and lung weights were observed after metalaxyl treatment. Although a single dose did not significantly affect the considered monooxygenases, a clear example of selective CYP3A induction was recorded in different tissues after repeated treatment. A 3 approximately -fold increase in CYP3A isozymes, probed by N-demethylation of aminopyrine, was observed in the liver (both sexes). Again, a 5 approximately -fold increase (averaged between male and female) in this oxidase activity was present in the kidney. No significant change of the selected biomarkers was observed in the lung. A weak, but significant reduction of CYP2B1 isoform in liver (male) was also recorded. Liver and kidney CYP3A overexpression was corroborated by means of Western immunoblotting analysis using rabbit polyclonal antibodies anti-CYP3A1/2. Northern blotting analysis with CYP3A cDNA biotinylated probe showed that, in the liver, the expression of this isozyme is regulated at the mRNA level. On the whole, these data seem to indicate the cotoxic and cocarcinogenic potential of this fungicide.

Alanine↗
PubMed1997

Molecular non-genetic biomarkers of effect related to acephate cocarcinogenesis: sex- and tissue-dependent induction or suppression of murine CYPs.

The aim of this work was to study the ability of the organophosphate insecticide acephate to alter some biochemical markers of effect related non-genetic cocarcinogenesis. For this purpose, selective CYP-dependent reactions have been examined in liver, kidney and lung microsomes of male and female Swiss albino CD1-mice treated (i.p.) with a 125 or 250 mg/kg b.w. dose of this pesticide. High specific substrates were used as a probe of various isozymes, such as CYP 1A1, 1A2, 2B1, 2E1 and 3A. Maked organ- and sex-related differences in either inducive or suppressive response by acephate depict a complex pattern of CYP modulation with the kidney being more responsive to 3A induction (up to 6.9-fold increase, male) and the lung to 2B1 suppression (up to 70% loss, mainly female). In the liver, a 2.7-fold increase in the 3A-like activity, probed by the O-demethylation of aminopyrine, in the O-deethylation of phenacetin (1.8-fold increase, 1A2), as well as in the hydroxylation of p-nitrophenol (1.6-fold increase, 2E1) was observed in male animals at a lower dose. In contrast, a marked reduction of CYP 1A1-mediated ethoxyresorfin O-deethylase activity ranging from 43% (lower dose) to 44% loss (higher dose) in female and male mice, respectively, and of CYP 2B1-mediated pentoxyresorufin O-dealkylase (3% loss, female) was achieved. In the kidney, an increase in the 'mixed' ethoxycoumarin O-deethylase (up to 2-fold) as well as in the 2B1-like activity (up to 2.8-fold) was also recorded in males at 250 mg/kg. Once again, in the lung, a different behaviour on 3A isoforms between female (approximately 2-fold increase) and male (44% loss) was seen at a lower dose. The specificity of CYP changes was corroborated by means of Western immunoblotting analysis using rabbit polyclonal antibodies, anti-CYP 3A1/2 and 2E1. Taken together, these data indicate a possible toxic/cotoxic, cocarcinogenic and promoting potential of acephate.

Animals↗
PubMed1997

Biomarkers of effect in evaluating dithianon cocarcinogenesis: selective induction and suppression of murine CYP3A isoform.

The ability of dithianon, whose mutagenic/cocarcinogenic activity has as yet not been clarified, to affect specific biomarkers of effect related to non-genotoxic cocarcinogenesis was investigated. For this purpose, several CYP-dependent reactions have been studied in liver, kidney and lung microsomes derived from male and female Swiss Albino CD1 mice treated i.p. with single (3 or 6 mg kg(-1) b.w.) or repeated (3 mg kg(-1) b.w., daily for 3 days) administrations of such fungicide. No significant changes in both absolute and relative liver, kidney and lung weights were achieved after dithianon treatment. Whereas a single dose was able to significantly induce certain monooxygenases, with repeated treatments a loss of activity was observed. For example, a approximately 2.4-fold increase of CYP3A-dependent activity, probed by N-demethylation of aminopyrine, was achieved in the liver (both sexes, lower dose) and, to a lesser extent, in lung. A small, but significant increase in the hydroxylation of p-nitrophenol (2E1) and in the O-deethylation of ethoxycoumarin (mixed) was also found in liver. With the exception of a approximately 46% loss in the 3A-like activity, no appreciable changes of the selected biomarkers were observed in kidney. Repeated dithianon doses were able to significantly reduce the 3A- and 2E1-dependent monooxygenases (approximately 30% and approximately 30% loss, respectively, averaged between male and female), as well as ethoxycoumarin O-deethylase activity (approximately 54% loss) in the liver. On the contrary, no significant CYP modulation in both kidney and lung was recorded. On the whole, dithianon has a complex pattern of CYP induction or suppression in various tissues of both sexes, suggesting the possible toxic/cotoxic and cocarcinogenic potential of this fungicide. These data can contribute to a better understanding of its toxicological profile, providing more information concerning the risk associated to human exposure.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1982

Chemical cocarcinogenesis with the use of a subclone derived from Balb/3T3 cells with catechol as cocarcinogen.

This study was performed for the detection of cocarcinogens by transformation in vitro with the use of a subclone of a Balb/3T3 cell line. Dose response, cytotoxicity, and transformation studies were done with the use of an indirect-acting carcinogen, benzo[a]pyrene (B[a]P), a direct-acting alkylating carcinogen, beta-propiolactone (BPL), and the mouse skin cocarcinogen catechol. The rate of transformation was notably higher in groups treated with B[a]P and catechol or BPL and catechol than in groups treated with either B[a]P or BPL. Catechol alone did not induce any transformation. All the cells isolated from the transformed foci showed characteristics of malignantly transformed cells, such as anchorage-independent growth. Thus chemical cocarcinogenesis was accomplished in vitro similar to that accomplished in in vivo studies reported earlier on mouse skin.

Animals↗
PubMed1975

Foreign-body tumorigenesis by vinyl chloride vinyl acetate copolymer: no evidence for chemical cocarcinogenesis.

We investigated whether vinyl chloride monomers, released from implants of vinyl chloride vinyl acetate copolymer (VCA), exerted cocarcinogenic activity and added thereby to the mechanism of foreign-body (FB) tumorigenesis. CBA/H and CBA/H-T6 mice were used. No evidence was found to indicate that chemical carcinogenic activity partakes in tumorigenesis by VCA implants. Hence it was concluded that VCA plastic is not suitable for the study of the combined process of FB/chemical cocarcinogenesis. Furthermore, experimental results obtained with VCA film implants were representative of FB tumorigenesis in the absence of demonstrable chemical carcinogenic activity.

Acetates↗
PubMed1978

Particle-enhanced membrane uptake of a polynuclear aromatic hydrocarbon: a possible role in cocarcinogenesis.

One possible mechanism by which cocarcinogenesis occurs was investigated. The effect of a particulate, silica, upon the rate of membrane uptake of a polynuclear aromatic hydrocarbon, benz[a]anthracene (BA), was studied. The fluorescence emission spectrum and quantum yield of BA, when adsorbed to silica, underwent spectral shifts upon addition of phospholipid vesicles. These spectral changes appeared to result from the transfer of BA from the silica surface into the lipid bilayer. We used these spectral changes to measure the rates of membrane uptake of BA from the silica-adsorbed state and from the crystalline and microcrystalline states of BA. Our studies demonstrated that adsorption of BA to silica resulted in an increased rate of uptake of BA into dipalmitoyl-L-alpha-phosphatidylcholine vesicles compared to the uptake rate into these vesicles from crystalling states. Such particle-enhanced membrane uptake of chemical carcinogens may be of importance in explaining the enhanced carcinogenicity of the polynuclear aromatic hydrocarbons in the presence of particulate matter.

Adsorption↗
PubMed1985

Test of catechol, tannic acid, Bidens pilosa, croton oil, and phorbol for cocarcinogenesis of esophageal tumors induced in rats by methyl-n-amylnitrosamine.

Catechol (CAS: 120-80-9), given in drinking water to rats, was the most effective of 5 phenols in enhancing [3H]thymidine incorporation [( 3H]dThd-l) into esophageal DNA. To test for esophageal cocarcinogenesis, groups of 30 male MRC-Wistar rats received 3 weekly ip injections of 25 mg methyl-n-amylnitrosamine [(MNAN) CAS: 13256-07-0]/kg. From the time of the first MNAN injection, each group also received catechol, tannic acid (CAS: 1401-55-4), dried leaves of Bidens pilosa L., or croton oil (CAS: 8001-28-3) (respectively, 2, 10, 50, and 2 g/kg semipurified diet), or were given 20 ip injections of 6 mg phorbol (CAS: 17673-25-5)/rat. The rats were killed after 20-45, 46-52, or 53-72 weeks (subgroups A, B, and C). In the group given MNAN alone, most esophageal papillomas developed during the first 45 weeks. Both catechol and B. pilosa significantly increased the esophageal papilloma multiplicity (No. of papillomas/rat) induced by MNAN, with a maximum tumor yield of 2.2 times that in the corresponding subgroup treated with MNAN alone. Papilloma multiplicity increased from subgroup A to subgroup C in the MNAN plus B. pilosa group but not in the MNAN plus catechol group. No tumors were induced by the test cocarcinogens given without MNAN. We concluded that a) an increased esophageal [3H]dThd-I indicates potential cocarcinogenicity and b) catechol and B. pilosa were weak esophageal cocarcinogens. These results support the view that catechol in cigarette smoke and B. pilosa as eaten in South Africa contribute to the etiology of human esophageal cancer.

Animals↗
PubMed1985

Cocarcinogenesis in vitro using Balb/3T3 cells and aromatic hydrocarbon cocarcinogens.

The mouse skin cocarcinogens fluoranthene, pyrene, and undecane were used with the indirect-acting carcinogen, benzo(a)pyrene (BP), and the direct-acting alkylating carcinogen, beta-propiolactone (BPL), in an in vitro transformation assay. Dose response, cytotoxicity, and transformation studies with these compounds were performed with a subclone (A31-1-1) of the Balb/3T3 cell line. Transformation frequencies were found to increase with increasing concentrations of BP used up to 1.0 micrograms/ml or when BPL was used up to 4.0 micrograms/ml. A significant increase (P less than 0.05) in the transformation frequency over that seen with carcinogen alone was observed when cells were exposed to a combination of fluoranthene (4.0 micrograms/ml) and BP (0.063 micrograms/ml) or pyrene (5.0 micrograms/ml) and BP (0.063 micrograms/ml). Thus, the transformation frequency obtained with BP + fluoranthene was 3.8 x 10(-4) compared to 1.2 x 10(-4) when BP was tested alone. Similarly, the transformation frequency using BP + pyrene was 2.8 x 10(-4) vs. 1.2 x 10(-4) when BP was tested alone. Undecane did not exert any cocarcinogenic effect with BP in the dose range tested. In this in vitro assay, no cocarcinogenic effect was observed when BPL was used with any of the above mouse skin cocarcinogens. All cells isolated from transformed foci showed characteristics of transformed cells including anchorage-independent growth.

Alkanes↗
PubMed1979

Ureterosigmoidostomy in rats: a model for the study of bladder tumour carcinogenesis and cocarcinogenesis.

A modified Coffey I ureterosigmoidostomy has been developed in rats as a model of urinary diversion for studying bladder carcinogenesis and co-carcinogenesis. Diverted and sham-operated animals were killed at 1, 3 and 6 months. Excretory urograms revealed minimal hydroureteronephrosis in most diverted animals. Upper tract bacterial colonisation was 9 times more frequent in diverted animals. Approximately one-third of the diverted animals had focal cortical scarring; however, renal function was normal in all groups as assessed by serum creatinine and electrolytes. These studies indicate that ureterosigmoidostomy in rats is a satisfactory model of urinary diversion for studying carcinogenesis.

Animals↗
PubMed1977

Epidermal intercellular relationships during carcinogenesis and cocarcinogenesis as revealed by scanning electron microscopy.

Investigations with the scanning electron microscope were carried out on the skin of 80 NMRI mice after treating them with small doses of the carcinogenic substance DMBA and the cocarcinogenic agent TPA, respectively. The results were correlated with histologic, transmission electron microscope and autoradiographic observations. The epidermis of TPA-treated animals was markedly hyperplastic with an orderly arrangement of cell layers. Autoradiographically only the basal cells were heavily labelled. With the scanning and transmission electron microscope a reduced number of intercellular connections and dilatation of the intercellular spaces could be detected. After treatment with DMBA the epidermis was only moderately hyperplastic but severely dysplastic with 3H-thymidine-labelled cells in the upper layers. The most characteristic findings were the loss of the intercellular connections, especially the lateral ones, and a pronounced dilatation of the intercellular spaces. The results obtained with the scanning electron microscope were quantified using morphometrical methods.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Possible role of acetaldehyde in ethanol-related rectal cocarcinogenesis in the rat.

Prospective epidemiologic studies have reported an increased risk of rectal cancer following chronic ethanol ingestion. The effect of ethanol on chemically induced colorectal carcinogenesis is controversial depending on the experimental conditions. In the present study the effect of chronic ethanol administration on acetoxymethylmethylnitrosamine-induced rectal cancer and the possible role of acetaldehyde in this process were investigated. Chronic ethanol administration resulted in an earlier occurrence of rectal tumors in this animal model. Because the concomitant administration of cyanamide, a potent acetaldehyde dehydrogenase inhibitor, showed a positive trend toward increased incidences of tumors, acetaldehyde could be involved in the ethanol-associated carcinogenesis. To measure colonic acetaldehyde, 12 chronically ethanol-fed and control rats received an acute dose of ethanol (2.5 g/kg body wt). The mucosal concentration of acetaldehyde was significantly higher in the rectum compared with the cecum (198 +/- 23 vs. 120 +/- 23 nmoles.g colon-1, p less than 0.05), but was not affected by chronic ethanol feeding. Furthermore, 6 germ-free rats had significantly lower acetaldehyde concentrations in the rectum (84 +/- 11 vs. 234 +/- 33 nmoles.g colon-1, p less than 0.01) and in the cecum (59 +/- 13 vs. 121 +/- 33 nmoles.g colon-1, p less than 0.05) compared with 6 conventional animals, and this was paralleled by the number of fecal bacteria in the 2 intestinal segments. In addition, to determine the effect of chronic ethanol feeding on colorectal cell turnover, 30 animals were pair-fed liquid diets. Using the metaphase-arrest technique, alcohol feeding induced rectal (19.1 +/- 2.0 vs. 9.1 +/- 1.8 cells.crypt-1.h-1, p less than 0.01), but not cecal (18.9 +/- 1.3 vs. 22.2 +/- 3.3 cells.crypt-1.h-1, p greater than 0.05) hyperregeneration. This was accompanied by an increase in the crypt proliferative compartment and increased mucosal ornithine decarboxylase activity (63 +/- 18 vs. 22 +/- 6 pmoles.hr-1.mg protein-1, p less than 0.05). The data show that chronic ethanol ingestion accelerates chemically induced rectal carcinogenesis and raise the possibility that acetaldehyde probably generated through bacterial ethanol oxidation may be involved in this process. The secondary hyperregeneration of the mucosa, observed after alcohol feeding, could by itself favour carcinogenesis.

Acetaldehyde↗
PubMed1996

Molecular non-genetic biomarkers related to Fenarimol cocarcinogenesis: organ- and sex-specific CYP induction in rat.

Selective biochemical markers of effect have been used to evaluate some non-genotoxic cocarcinogenic properties of Fenarimol. Several CYP-dependent reactions have been monitored in liver, kidney and lung microsomes of male and female Sprague-Dawely rats treated (i.p.) with 200 or 400 mg/kg body wt dose of this pesticide. Highly specific substrates were used as probes of various isoforms, such as CYP1A1, 1A2, 2B1, 2E1 and 3A. A complex pattern of CYP induction, including organ- and sex-related differences in the inductive response by Fenarimol, has been recorded in this investigation, the kidney (mainly male) being more responsive when compared to other tissues. A 6.6-fold increase in the 2B1-like activity, probed by dealkylation of pentoxyresorufin was observed in the liver at a higher dose. On the contrary, a marked induction of CYP1A1 mediated ethoxyresorufin O-deethylase activity, ranging from 20- to 35-fold in female and male, respectively, was observed in the kidney at a lower dose tested. In the lung, at a higher dose, the p-nitrophenol hydroxylase activity (2E1) was enhanced up to 3.5-fold in male animals, whereas the 3A-like activity, probed by the N-demethylation of aminopyrine, was induced up to 2.6-fold in females. A weak, although significant reduction of CYP2B1 isoforms in lung was also recorded. Taken together, these data corroborated by means of Western immunoblotting analysis (using rabbit polyclonal antibodies anti-CYP 2B1/2, 1A1, 2E1, and 3A1/2) indicate a possible cotoxic, comutagenic cocancerogenic and promoting potential of this fungicide.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1979

Cocarcinogenesis.

Explore the source record for details and available documents.

2-Acetylaminofluorene↗
PubMed1999

Molecular non-genetic biomarkers of effect related to methyl thiophanate cocarcinogenesis: organ- and sex-specific cytochrome P450 induction in the rat.

We used selective biochemical markers of effect to evaluate some non-genotoxic cocarcinogenic properties of methyl thiophanate (MTH) associated with cytochrome P450 (CYP) changes. Several CYP-dependent reactions were monitored in the liver, kidney and lung microsomes of male and female Sprague-Dawley rats treated (i.p.) with a single (285 or 570 mg/kg body weight) or repeated (daily 285 or 570 mg/kg body weight for three consecutive days) doses of this pesticide. No significant changes in absolute or relative liver, kidney and lung weights were observed after MTH injection. Highly specific substrates were used as probes of different isoforms, such as CYP1A1, 1A2, 2B1, 2E1 and 3A. A complex pattern of CYP induction, including organ- and sex-related differences, was observed, particularly in the liver (CYP3A, 2B1), kidney (CYP1A1, 2E1) and lung (CYP3A, 1A1). In the liver, an increase up to 29-fold in the 2B1-like activity, probed by the O-dealkylation of pentoxyresorufin, was observed at lower dose in both sexes, and the induction of CYP 1A2-mediated methoxyresorufin O-demethylase activity (up to 3.6-fold) was recorded at the higher dose in males. In the kidney, the O-deethylation of ethoxyresorufin (CYP1A1-linked) was increased up to 28.2-fold and the CYP2E1-dependent p-nitrophenol hydroxylases were enhanced up to 6.3-fold in females receiving higher multiple MTH administration. In the lung, the CYP3A-associated activity was the most induced oxidases, as exemplified by the marked increase in the O-demethylation of aminopyrine (up to 3.6-fold) in males. A weak, although significant, reduction of CYP2B1-linked oxidases was also observed in repeated treatment in the kidney (males) and lung (females). These results suggest that the induction of CYP-catalyzed drug metabolism by prolonged exposure to MTH may result in accelerated metabolism of coadministered drugs with important implications for their disposition Together with an alteration of endogenous metabolism, the adverse effects associated with CYP changes such as toxicity/cotoxicity, cocarcinogenicity and promotion may also have clinical consequences.

Animals↗