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61.
Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung 总被引:1,自引:0,他引:1
Prahalad AK; Ross JA; Nelson GB; Roop BC; King LC; Nesnow S; Mass MJ 《Carcinogenesis》1997,18(10):1955-1963
Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic
hydrocarbon, is the most potent carcinogen ever tested in mouse skin and
rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction,
tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in
strain A/J mouse lung. Groups of mice received a single i.p. injection of
0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment,
DNA adducts were measured at times between 1 and 28 days, while tumors were
counted at 250 days and analyzed for the occurrence of point mutations in
codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung
induced six major and four minor DNA adducts. Maximal levels of adduction
occurred between 5 and 10 days after injection followed by a gradual
decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti-
and syn-11,12- dihydroxy-13,14-epoxy-
11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both
deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed
by cochromatography. The major adduct was identified as a product of the
reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced
significant numbers of lung adenomas in a dose- dependent manner, with the
highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In
tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based
on the administered dose, DB[a,l]P was more active than other environmental
carcinogens including benzo[a]pyrene. As a function of time-integrated DNA
adduct levels, DB[a,l]P induced lung adenomas with about the same potency
as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar
in carcinogenic potency to other PAHs in the strain A/J mouse lung model.
Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors
revealed the predominant mutations to be G-->T transversions in the
first base of codon 12, A-->G transitions in the second base of codon
12, and A-->T transversions in the second or third base of codon 61,
concordant with the DNA adduct profile.
相似文献
62.
Nesnow S; Davis C; Nelson G; Ross JA; Allison J; Adams L; King LC 《Carcinogenesis》1997,18(10):1973-1978
C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study the in
vitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) and
benzo[a]pyrene (B[a]P). The morphological transforming activities of these
rodent carcinogens were compared using replicate concentration- response
studies. In concentration ranges where both polycyclic aromatic
hydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12 times as
potent as B[a]P based on concentration. At lower concentrations DB[a,l]P
was active at 0.10 and 0.20 microM, concentrations where B[a]P was
inactive. This makes DB[a,l]P the most potent non-methylated PAH evaluated
to date in C3H10T1/2 cells. DNA adducts of DB[a,l]P in C3H10T1/2 cells were
analyzed by both TLC and TLC/HPLC 32P-postlabeling methods using
mononucleotide 3'-phosphate adduct standards derived from the reactions of
anti-DB[a,l]P-11,12-diol- 13,14-epoxide (anti-DB[a,l]PDE) and
syn-DB[a,l]P-11,12-diol-13,14- epoxide (syn-DB[a,l]PDE) with deoxyadenosine
3'-monophosphate and deoxyguanosine 3'-monophosphate. All of the DNA
adducts observed in C3H10T1/2 cells treated with DB[a,l]P were identified
as being derived from the metabolism of DB[a,l]P to its fjord region diol
epoxides through DB[a,l]P-11,12-diol. The predominant adduct was identified
as an anti-DB[a,l]PDE-deoxyadenosine adduct. Other major adducts were anti-
DB[a,l]PDE-deoxyguanosine and syn-DB[a,l]PDE-deoxyadenosine adducts with
minor amounts of syn-DB[a,l]PDE-deoxyguanosine adducts. These DNA adduct
data are consistent with similar findings of DB[a,l]PDE- deoxyadenosine
adducts in mouse skin studies and human mammary cells in culture.
相似文献
63.
Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver 总被引:2,自引:0,他引:2
Dichloroacetic acid (DCA) is a chlorination byproduct found in finished
drinking water. When administered in drinking water this chemical has been
shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over
the animal's lifetime. In this study, we investigated whether mutant
frequencies were increased in mouse liver using treatment protocols that
yielded significant tumor induction. DCA was administered continuously at
either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice
harboring the bacterial lacI gene. Groups of five or six animals were
killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of
treatment, there was no significant difference in mutant frequency between
the treated and control animals at either dose level. At 60 weeks, mice
treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency
over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60
weeks had a 2.3-fold increase in mutant frequency over the concurrent
controls (P = 0.002). The mutation spectrum recovered from mice treated
with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%)
and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T
transitions comprised 53.19% of the recovered mutants among control
animals. Although only 19.15% of mutations among the controls were at T:A
sites, 32.79% of the mutations from DCA-treated animals were at T:A sites.
This is consistent with the previous observation that the proportion of
mutations at T:A sites in codon 61 of the H-ras gene was increased in
DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates
DCA-associated mutagenicity in the mouse liver under conditions in which
DCA produces hepatic tumors.
相似文献
64.
65.
66.
Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats 总被引:4,自引:1,他引:4
Harris AJ; Shaddock JG; Manjanatha MG; Lisenbey JA; Casciano DA 《Carcinogenesis》1998,19(8):1451-1458
Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is
a contaminant of the human food supply, particularly in parts of Africa and
Asia. AFB1-induced changes in gene expression may play a part in the
development of the toxic, immunosuppressive and carcinogenic properties of
this fungal metabolite. An understanding of the-role of AFB1 in modulating
gene regulation should provide insight regarding mechanisms of AFB1-induced
carcinogenesis. We used three PCR- based subtractive techniques to identify
AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential
display PCR (DD-PCR), representational difference analysis (RDA) and
suppression subtractive hybridization (SSH). Each of the three techniques
identified AFB1- responsive genes, although no individual cDNA was isolated
by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH
were found to represent eight genes that are differentially expressed as a
result of AFB1 exposure. Genes whose mRNA levels were increased in cultured
primary rat hepatocytes after AFB1 treatment were corticosteroid binding
globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin,
C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase
Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels
after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When
liver RNA from AFB1-treated male F344 rats was evaluated for transferrin,
CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and
an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen.
Analysis of the potential function of these genes in maintaining cellular
homeostasis suggests that their differential expression could contribute to
the toxicity associated with AFB1 exposure.
相似文献
67.
S.G. Brouwer de Koning T.P. ter Braak F. Geldof R.L.P. van Veen M.J.A. van Alphen L.H.E. Karssemakers W.H. Schreuder M.B. Karakullukcu 《International journal of oral and maxillofacial surgery》2021,50(3):287-293
In mandibular surgery, three-dimensionally printed patient-specific cutting guides are used to translate the preoperative virtually planned resection planes to the operating room. This study was performed to determine whether cutting guides are positioned according to the virtual plan and to compare the intraoperative position of the cutting guide with the resection performed. Nine patients were included. The exact positions of the resection planes were planned virtually and a patient-specific cutting guide was designed and printed. After surgical placement of the cutting guide, intraoperative cone beam computed tomography (CBCT) was performed. Postoperative CT was used to obtain the final resection planes. Distances and yaw and pitch angles between the preoperative, intraoperative, and postoperative resection planes were calculated. Cutting guides were positioned on the mandible with millimetre accuracy. Anterior osteotomies were performed more accurately than posterior osteotomies (intraoperatively positioned and final resection planes differed by 1.2 ± 1.0 mm, 4.9 ± 6.6°, and 1.8 ± 1.5°, respectively, and by 2.2 ± 0.9 mm, 9.3 ± 9°, and 8.3 ± 6.5° respectively). Differences between intraoperatively planned and final resection planes imply a directional freedom of the saw through the saw slots. Since cutting guides are positioned with millimetre accuracy compared to the virtual plan, the design of the saw slots in the cutting guides needs improvement to allow more accurate resections. 相似文献
68.
van Aar F Schreuder I van Weert Y Spijker R Götz H Op de Coul E The Partner Notification Group F 《BMC infectious diseases》2012,12(1):114
ABSTRACT: BACKGROUND: Partner notification (PN) among individuals newly diagnosed with HIV/STI is seen as a vital tool to identify others at risk of infection. However, hardly any data are available on the effectiveness of PN on HIV/STI transmission in the Netherlands. This study aims to fill this gap by assessing current PN practices, case-finding effectiveness, and determinants of being notified among men having sex with men (MSM) in the Netherlands. METHODS: Nurses from five STI centers participated in a prospective pilot study on PN outcomes (partners being: at risk, notifiable, notified, and tested) for HIV/STI, by completing a newly developed PN registration form (PN database). PN outcomes including case-finding effectiveness (number of newly diagnosed cases in partners/number of partners being tested) for HIV, syphilis, and gonorrhoea were studied among MSM. Furthermore, the national STI database was analyzed to identify determinants of being notified. The number of infections that remained undetected was estimated based on these two databases. RESULTS: In total 105 MSM, newly diagnosed with HIV/STI, reported 612 sexual partners at risk of whom 41% were notifiable and 31% were notified. Patient referral was the predominant PN method (90%). The overall case-finding percentage was 36% (HIV: 15-33%, gonorrhoea: 17- 50% and syphilis: 4-11%). Case-finding percentages were lower in the national STI database: 21% (5%, 28%, 12%). Persons with one or more sexual partners, known HIV positives, and IDU were more likely to be notified to the STI clinic. Notified clients were more likely to have HIV/STI than unnotified clients (OR 1.7-2.5). Based on these two databases, an estimated 75 to 133 infections remained undetected (HIV: 12-90; gonorrhoea: 28-97; syphilis: 5-12 infections). CONCLUSIONS: Partner notification among MSM in the Netherlands is suboptimal; an extensive number of STI/HIV infections remained undetected mainly due to unnotifiable partners. To enhance PN practices, combined and innovative PN interventions such as Internet-based PN will be implemented for hard-to-reach MSM and other risk groups. 相似文献
69.
70.
Ante Prki? Christiaan JA van Bergen Bertram The Denise Eygendaal 《World journal of orthopedics》2016,7(1):44-49
The elbow joint is a complex joint, which, when impaired in function, leads to severe disability. In some cases however, an arthroplasty might be an appropriate treatment. In the past four decades, large steps havebeen taken to optimize this treatment in order to achieve better post-operative outcomes. To understand these progresses and to discover aspects for upcoming improvements, we present a review on the past developments, the present state of affairs and future developments which may improve patient care further. 相似文献