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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the activity and associated kinetic parameters of epidermal protein kinase C (PKC) following stimulation by sn-1,2-dioctanoylglycerol (DIC8) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and to examine the relationship between levels of epidermal PKC activity and the induction of ornithine decarboxylase by these agents, utilizing various stocks and strains of mice. Importantly, the mouse strains and stock used in this study have known differing susceptibilities to undergo TPA-induced tumor promotion: the CD-1 stock and the DBA/2 strain (both sensitive to TPA-induced tumor promotion) and the C57BL/6 strain (resistant to TPA-induced tumor promotion). TPA-stimulated protein kinase C activity was measured in the 10(5)g supernatant fraction of epidermal homogenates using lysine-rich histone as a phosphate acceptor substrate. The maximal velocities for TPA-stimulated epidermal PKC activity in CD-1, DBA/2 and C57BL/6 were 0.28, 0.29 and 0.27 nmol PO4-histone/mg 10(5)g protein/min, respectively. TPA-stimulated epidermal PKC from CD-1, DBA/2 and C57BL/6 had similar theoretical Vmax values and the apparent concentrations of TPA yielding half-maximal stimulation of PKC were also similar. DiC8-stimulated PKC activity to a greater Vmax; however, the concentration required to yield half-maximal stimulation of PKC was one thousand times greater than that of TPA. There were no strain differences in these parameters when the enzyme was stimulated with DiC8. Thus, the levels of epidermal PKC activity in CD-1, DBA/2 and C57BL/6 mice exhibit no strain differences when stimulated by TPA or DiC8 using lysine-rich histone as a phosphate acceptor substrate. Since sn-1,2-diacylglycerols are known effective inducers of epidermal ornithine decarboxylase (ODC) activity, the induction of epidermal ODC was examined in each mouse strain 5 h after topical application of 2 nmol TPA, 5 nmol TPA or 2.5 mumol DiC8. After topical treatment with TPA, C57BL/6 demonstrated an unexpected 2- and 4-fold increase in ODC activity over CD-1 and DBA/2 mice. After treatment with DiC8, C57BL/6 demonstrated a 6- and 10-fold increase in ODC activity over CD-1 and DBA/2, respectively. Thus, the resistant strain (C57BL/6) demonstrated a 'hyperinducibility' of epidermal ODC activity by TPA or DiC8. The time course for the induction of epidermal ODC was examined in each strain, and at every time point measured (3-15 h), the C57BL/6 strain exhibited this 'hyperinducibility' of ODC relative to the other strains. Epidermal DNA synthesis was stimulated to a similar extent in C57BL/6 and CD-1 mice.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1989 May
PMID:Comparison of epidermal protein kinase C activity, ornithine decarboxylase induction and DNA synthesis stimulated by TPA or dioctanoylglycerol in mouse strains with differing susceptibility to TPA-induced tumor promotion. 270 40

Transplacental effect of cobalamin coenzyme, adenosylcobalamin (Adocbl), on the carcinogenic action of N-nitroso-N-ethylurea (ENU) was studied in culture of the mouse embryonic kidney tissue by histoautoradiography. Coenzyme methylmalonyl-CoA-mutase, Adocbl, injected into DBA/2 mice in the prenatal period did not stimulate the proliferative activity of epithelial cells of the embryonic kidney. The treatment with Adocbl did not intensify hyperplastic changes common for the early stages of carcinogenesis. The frequency of hyperplastic changes mainly of focal proliferation in kidney explants with the combined administration was considerably lower than with the isolated action of the carcinogen and amounted to 8.7% and 21.5%, respectively (P less than 0.001).
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PMID:[The modifying influence of adenosylcobalamin on the transplacental carcinogenic effect of N-nitroso-N-ethylurea in organ cultures of the kidneys of DBA/2 mice]. 275 37

Mouse vaccination with alive endogenous N-tropic virus OA-3 inhibited and decreased the development of the Rauscher leukemia in C57B1/6 mice (B-type) and SWR mice (N-type) as well as the development 7,12-dimethyl benzanthracene (DMBA)-induced tumours in mouse hybrids (neither N-, nor B-types). The effect of vaccination was DMBA- or MLV-P-dose-dependent. Vaccination with the same virus did not affect the incidence of gamma-irradiation-induced leukemia in CBA mice (N-type) and C57B1/6 mice while it increased twice the incidence of radiation leukemia in DBA mice (N-type). However, the incidence of thymomas lowered in radiation leukemia-bearing vaccinated mice of all the 3 strains, which may result from inhibition of murine thymotropic endogenous virus reproduction. The data obtained indicate the participation of murine own endogenous viruses in DMBA- or gamma-irradiation induced carcinogenesis.
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PMID:[Effect of vaccination of mice with endogenous retrovirus on the development of tumors induced by gamma-irradiation or 7,12-dimethylbenz[a]anthracene]. 302 58

The effects of multiple applications of 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 6.8 nmol), teleocidin (6.8 nmol), 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin, 220 nmol), mezerein (6.8 nmol), 4-O-Methyl-TPA (4-O-Me-TPA, 150 micrograms) and benzoyl peroxide (BzP, 20 mg) on the skin of DBA/2 and C57BL/6 mice were studied histologically. After four applications of TPA given over a 2-week period, the epidermis of DBA/2 mice showed a marked epidermal hyperplasia and the presence of a much greater number of dark basal keratinocytes (DCs) 48 h after the last treatment compared with C57BL/6 mice treated with a similar dose and protocol. A marked dermal infiltration of polymorphonuclear leukocytes (PMNs) was observed in DBA/2 mice 48 h after the last application of TPA, whereas little PMN infiltration was observed in skin of C57BL/6 mice. At 96 h after the last application of TPA, DBA/2 mice still showed a much greater degree of epidermal hyperplasia than C57BL/6 mice. PMNs were virtually absent in the dermis of both DBA/2 and C57BL/6 mice by 96 h after the last TPA treatment. Interestingly, treatment of both strains of mice with multiple applications of teleocidin induced a marked epidermal hyperplasia, a high percentage of DCs and a high labeling index (LI), similar to that observed in DBA/2 mice 48 h after the last treatment. Chrysarobin (given once-weekly for 4 weeks) induced a moderate sustained hyperplasia and DC response 48 h after the last treatment in both DBA/2 and C57BL/6 mice; however, C57BL/6 mice showed a greater epidermal hyperplasia than DBA/2 mice. Chrysarobin induced a significant infiltration of PMNs into the dermis of DBA/2 mice whereas in C57BL/6 mice there was only a slight dermal infiltration of PMNs. Mezerein (given twice-weekly for 2 weeks) induced a moderate epidermal hyperplasia, DC response and LI of similar magnitude in both DBA/2 and C57BL/6 mice, but did not induce PMN infiltration in either strain. BzP and 4-O-Me-TPA (given twice-weekly for 2 weeks) induced only a weak sustained epidermal hyperplasia, DC response and LI of similar magnitude in both strains of mice, and there was little, if any, dermal infiltration of PMNs either 48 or 96 h after the last treatment. Examination of the relationship between the extent of induced hyperplasia and the DC response showed an excellent linear correlation whereas the extent of PMN infiltration into the dermis was not well correlated with either parameter.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1987 Dec
PMID:Comparison of the histological changes in the skin of DBA/2 and C57BL/6 mice following exposure to various promoting agents. 311 44

The frequency of micronucleated erythrocytes (MNE) in 3 inbred mouse strains and 2 of their hybrids (C57BL/6, BALB/c, DBA/2, BDF1 and CDF1) were examined after polycyclic aromatic hydrocarbons (PAHs; 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (3-MC), benzo[a]pyrene (BaP), benzo[e]pyrene (BeP) and anthracene (ANT] were injected i.p. PAHs are thought to form active metabolites after being administered to mammals. In mouse strains with inducible PAH activating enzymes, such as C57BL/6 or BALB/c, MNE were significantly induced, as compared to control mice, 48 h after DMBA, BaP, or 3-MC was injected. No increase in the frequency of MNE occurred in the DBA/2 strain which cannot induce the activating enzymes. BeP and ANT did not increase the frequency of MNE in any mouse used. The levels of MNE induction in BDF1 or CDF1 hybrids were similar to those in C57BL/6 or BALB/c. These results support the view that the genetic capacity to metabolize PAHs is strongly associated with micronucleus induction as in the case of PAH carcinogenesis.
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PMID:Mouse strain differences in the induction of micronuclei by polycyclic aromatic hydrocarbons. 312 1

Since current evidence suggests that the tumor promotion stage is a primary determinant in susceptibility to multistage carcinogenesis, we have characterized the genetics of susceptibility to phorbol ester skin tumor promotion in inbred mice. Susceptibility of hybrids (B6D2F1), between DBA/2 (sensitive) and C57BL/6 (resistant) parents, initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) was similar to DBA/2 mice at doses of 13.6 nmol per mouse but clearly less when doses of 1.7-6.8 nmol per mouse were used. In addition, no significant differences were observed between male and female B6D2F1 mice in terms of tumor incidence although some differences were observed in tumor multiplicities between male and female F1 mice at the highest TPA dose. Reciprocal F1 mice initiated with DMBA (i.e. D2B6F1) were also responsive to TPA. Female D2B6F1 mice were of lower sensitivity at lower doses of TPA, compared to female DBA/2, a finding similar to that observed with B6D2F1 mice initiated with MNNG. Further analyses of the susceptibility of B6D2F2 and B6D2F1 X C57BL/6 backcross mice to TPA promotion indicated that more than one dominant genetic locus must account for the differences in promotion sensitivity between DBA/2 and C57BL/6 mice. To understand further the genes responsible for promotion sensitivity, histological evaluations were performed on DBA/2, C57BL/6 and B6D2F1 mice. Histological examination revealed that the epidermis of DBA/2 mice showed a marked hyperplasia and the presence of a much greater number of dark basal keratinocytes (DCs) compared with C57BL/6 mice 48 h after the last of four applications of TPA (doses greater than or equal to 3.4 nmol). A marked dermal infiltration of polymorphonuclear leukocytes (PMNs) was observed in DBA/2 mice, whereas little infiltration was observed in the skin of C57BL/6 mice. The hyperplasia in the skin of B6D2F1 mice was intermediate between DBA/2 and C57BL/6 mice at all TPA doses examined except the lowest dose (1.7 nmol), whereas the DC response, although significantly lower at doses of 6.8 nmol or below, was similar to DBA/2 mice at higher TPA doses (13.6 and 17.0 nmol). The infiltration of PMNs in the dermis of B6D2F1 mice was similar to or greater than DBA/2 mice at all doses of TPA tested.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1988 Apr
PMID:Susceptibility to phorbol ester skin tumor promotion in (C57BL/6 x DBA/2) F1 mice is inherited as an incomplete dominant trait: evidence for multi-locus involvement. 312 9

Growth of established murine tumor lines in media containing the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), was associated with reversible reductions in sensitivity to in vitro and in vivo parameters of natural resistance. L5178Y-F9 cells exposed to 100 ng TPA/ml for 2 days and returned to culture without TPA for 0-2 days, exhibited reductions in sensitivity to complement-mediated lysis by natural antibodies (Nab), activated macrophages and hypotonic lysis. The natural killer (NK) cell sensitive SL2-5 lymphoma was less sensitive to NK cells, complement-dependent NAb and hypotonic lysis after 2 days growth in 2 or 3 micrograms TPA/ml. Although TPA-treated L5178Y-F9 cells could acquire higher levels of serum NAb in vitro, this was complicated by the instability of the binding at 37 degrees C resulting in an effectively reduced capacity to bind NAb which was also demonstrated by TPA-treated SL2-5 cells. The tumor frequency of threshold s.c. inocula and the i.v. metastatic potential of the TPA-treated tumors was increased in syngeneic DBA/2 mice revealing possible correlations between reductions in the cellular characteristics assayed in vitro and decreased susceptibility to host-mediated defenses in vivo. Continued growth of the TPA-treated cells for a total of 2-8 days without TPA produced a reversal in the in vitro parameters, in the tumor frequency and in the metastatic potential, indicating the requirement for TPA to maintain the resistant phenotype. These data are consistent with the initial reversible nature of the promotion phase of multistage carcinogenesis. The reversible TPA-induced reductions in sensitivity to mediators of natural resistance may be an integral component of promotion, contributing to tumor survival in vivo and increasing the probability that the tumor will progress to a more malignant phenotype.
Carcinogenesis 1988 Nov
PMID:Tumor progression in vitro: tumor-promoter-induced reversible decrease in natural immune susceptibility. 318 Mar 34

The abilities of sn-1,2-didecanoylglycerol (sn-1,2-DDG) to induce epidermal ornithine decarboxylase (ODC) activity and epidermal hyperplasia were tested using SENCAR, DBA/2 and C57BL/6 mice. Following a single application of 5000 nmol of sn-1,2-DDG, ODC activity reached a maximum at 4 h after treatment with a peak activity of 6.03 nmol CO2/mg protein/60 min in C57BL/6, 1.50 in SENCAR and 0.73 in DBA/2, respectively. The time course and magnitude for induction of ODC activity after multiple treatments was very similar to that after a single application in these three mouse lines. Interestingly, the induced ODC activity in C57BL/6 was always higher than that in SENCAR and DBA/2 mouse epidermis regardless of the treatment protocol. Induction of hyperplasia and dark basal keratinocytes (DCs) and changes in the labeling index (LI) of basal keratinocytes in DBA/2 and C57BL/6 mice following treatment with sn-1,2-DDG were investigated. Multiple treatments (twice weekly for 2 weeks) of 5000 nmol sn-1,2-DDG did not induce substantial increases in epidermal thickness or DCs 24 or 48 h after the last treatment. In contrast, TPA induced a marked increase in epidermal thickness in DBA/2 rather than C57BL/6 and a considerably higher induction of DCs in DBA/2 (37.3 +/- 2.2%) than in C57BL/6 (9.6 +/- 2.5%) 48 h after the last treatment. The LIs after topical application of sn-1,2-DDG were elevated at 24 h, but returned to basal levels by 48 h in both strains, whereas TPA treatment significantly elevated the LI in both strains at 48 h after the last application. In addition, the effects of various doses and frequencies of application of sn-1,2-DDG were investigated using SENCAR mice. High doses (20,000 nmol) or more frequent applications (5000 nmol once daily for 7 days) of sn-1,2-DDG still produced only weak hyperplasia. These results suggest that the induction of epidermal ODC activity can be dissociated from the induction of epidermal hyperplasia and may provide an explanation for the lack of complete promoting activity presently observed with membrane permeable diacylglycerol derivatives.
Carcinogenesis 1988 Dec
PMID:sn-1,2-didecanoylglycerol effectively induces epidermal ornithine decarboxylase but only weak hyperplasia in mouse skin. 319 67

Dependence of polycyclic aromatic hydrocarbon (PAH)-induced mutagenicity on the bay region of the molecule and on the activating cytochrome P-450 enzyme was studied. Eleven PAHs with and six without a bay region were activated by postmitochondrial supernatants from control and 3-methylcholanthrene (MC)-pretreated C57BL/6 mice and from control, MC- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-pretreated DBA/2 mice and from control and MC-pretreated Sprague-Dawley and Lewis rats. S-9 fractions from MC- or TCDD-treated animals induced more mutagenicity with PAHs with a bay region compared with S-9 fractions from control animals or MC-treated D2 mice. Mutagenicities of PAHs without a bay region were largely independent of the source of activating enzyme. There were three exceptions, namely benzo[e]pyrene, phenanthrene and perylene (each possessing a bay region), which were not mutagenic. These studies support the notion that the Ah-locus-controlled induction of cytochrome P1-450 activating PAHs into reactive intermediates at the bay region of the hydrocarbon molecule is of prime importance in the mutagenicity of PAHs. Qualitative correspondence to carcinogenicity is also apparent.
Carcinogenesis 1987 Jun
PMID:Mutagenicity studies of different polycyclic aromatic hydrocarbons: the significance of enzymatic factors and molecular structure. 330 Oct 44

DBA/2, BALB/c or (BALB/c X DBA/2)F1 (CDF1) mice of both sexes were treated for 1 week with a dietary hepatocarcinogenic tryptophan pyrolysate component (Trp P-1 or Trp P-2), and the activity of hepatic microsomal enzyme(s) for mutagenic activations of Trp P-1 and Trp P-2 were assessed by means of a mutation test with Salmonella typhimurium TA98. In both Ah-responsive (BALB/c and CDF1) and Ah-nonresponsive (DBA/2) mice, the dietary treatment with Trp P-1 or Trp P-2 resulted in a significant increase of the enzyme activity for mutagenic activations of Trp P-1 and Trp P-2 in females but not in males, except the case of male BALB/c mice treated with dietary Trp P-1. Also induction of enzyme(s) in female mice was suppressed by an administration of testosterone. The induced hepatic microsomal enzyme(s) was demonstrated to be cytochrome P-450 isozyme(s) (mol. wt of 55,000 daltons) by immunoblots with use of an anti-rat cytochrome P-448 monoclonal antibody and by selective inhibition of the activity by addition of 7,8-benzoflavone into the mutation assay system. These findings indicate that carcinogenic aromatic amines such as Trp P-1 and Trp P-2 are able to induce hepatic cytochrome P-450 isozyme(s) not only in Ah-responsive mice (BALB/c and CDF1) but also in Ah-nonresponsive DBA/2 mice and that the cytochrome P-450 induction is controlled by androgen(s).
Carcinogenesis 1988 Apr
PMID:Hepatic cytochrome P-450 isozyme(s) induced by dietary carcinogenic aromatic amines preferentially in female mice of DBA/2 and other strains. 335 64


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