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R Mustonen

Publications and source records attributed to R Mustonen.

32 records · Page 2Linked to original sources
PubMed1990

32P-postlabeling of 7-methylguanine adducts in DNA.

The 32P-postlabeling technique introduced by Randerath and co-workers has been particularly successful with stable and nonpolar DNA adducts, but the assay has not been used to any large extent to detect 7-alkylguanine derivatives. In the present communication, we have investigated the phosphorylation reaction by T4 polynucleotide kinase using 7-methyl-3'-dGMP, ring-opened 7-methyl-3'-dGMP and enzyme-digested methylated DNA as substrates. The methylated substrates were detected at femtomol (fmol) sensitivities. 7-methyl-3'-dGMP was quantitatively phosphorylated at these low concentrations. The efficiency of phosphorylation of the ring-opened product was less. It was shown that ring-opened 7-methyl-3'-dGMP was resistant to digestion with nuclease P1, making alkali-treatment and enzyme digestion of DNA possible approaches to the determination of 7-methylguanine in DNA.

Animals↗
PubMed1990

32P-postlabelling of 7-methyl-dGMP ring-opened 7-methyl-dGMP and platinated dGpdG.

The 32P-postlabelling technique introduced by Randerath and coworkers was used to investigate the efficiency of the phosphorylation reaction by T4 polynucleotide kinase using three synthesized adducts: 7-methyl-dGMP, ring-opened 7-methyl-dGMP and platinated dGpdG. The methylated substrates were detected at sub-fmol sensitivities. 7-Methyl-dGMP was quantitatively phosphorylated at these low concentrations. The efficiency of phosphorylation of the ring-opened product was less (about one order of magnitude) and that of Pt(dGpdG) about three orders of magnitude less. These results show that T4 polynucleotide kinase phosphorylation is an efficient reaction with 7-methyl-dGMP and with ring-opened 7-methyl-dGMP, even though in the latter case longer incubation times may have to be used to boost the reaction towards completion. By contrast, the low level of phosphorylation with Pt(dGpdG) does not appear encouraging for quantitative determination requiring a high sensitivity.

Deoxyguanine Nucleotides↗
PubMed1989

Determination of cis-diamminedichloroplatinum (II) in plasma proteins and hemoglobin of cancer patients.

A study was conducted to determine the levels of cis-diamminedichloroplatinum (II) (cisplatin) in plasma proteins and hemoglobin of cancer patients after cisplatin chemotherapy. Thirty-seven cancer patients with different type of cancers (lung, esophageal, urinary tract, and testicular cancer, melanoma, osteosarcoma etc) received cisplatin 32-110 mg/m2 either as a single intravenous infusion or as infusions given on 5 consecutive days. Blood samples were classified according to time from previous cisplatin infusion. They included a total of 103 samples taken before the cisplatin infusion, immediately after infusion, 1, 2 or 3-5 days after infusion or 2-3, 4, or 5-7 weeks after infusion. Platinum (Pt) concentration in plasma proteins and hemoglobin was measured by atomic absorption spectroscopy (AAS). The data showed a correlation between the dose of cisplatin and the concentrations of Pt in plasma proteins and hemoglobin of cancer patients. Plasma proteins bound more cisplatin than hemoglobin, the respective maxima in the patients receiving greater than 50 mg/m2 being 27.7 and 1.6 ng/mg protein in samples drawn immediately after treatment. The kinetics of disappearance of Pt from plasma proteins showed several components; the initial half-life was about 5-7 days. The disappearance of Pt from hemoglobin showed a single component of a half-life of 12-14 days.

Adolescent↗
PubMed1989

Effects of commercial chlorophenolate, 2,3,7,8-TCDD, and pure phenoxyacetic acids on hepatic peroxisome proliferation, xenobiotic metabolism and sister chromatid exchange in the rat.

The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100 mg/kg/day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05-5 micrograms/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 micrograms/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly.

Animals↗
PubMed1989

Dose-dependence and stability of cisplatin binding to tissue DNA and blood proteins in rats.

Two experiments were carried out by using atomic absorption spectroscopy on the stability and dose-dependence of cisplatin [cis-diamminedichloroplatinum (II)] binding to blood proteins and tissue DNA of male Han/Wistar rats. The dose-dependence was studied by injecting 17 rats i.p. either with cisplatin (4.4, 8.0 or 11.0 mg/kg) or 0.9% NaCl (controls). The Pt concentrations in blood proteins (plasma proteins and hemoglobin) and DNAs of different tissues (kidney, liver, lung and testis) were measured 24 h after the treatment. The binding of cisplatin to blood proteins and tissue DNAs correlated with each other and the dose. The stability was studied by treating 17 rats i.v. with 8.0 mg cisplatin/kg. The Pt concentrations in kidney, liver and lung DNA were determined 5 h, 1, 3 or 5 days after the treatment. The disappearance of Pt was faster in kidney DNA than in liver or lung DNA; in 5 days the Pt concentration in kidney DNA decreased by 63% while the Pt content in liver or lung decreased by 40%. Both of these experiments showed that the binding of cisplatin to kidney DNA exceeded the other tissue DNAs examined. Testicular DNA showed the lowest level of binding. The present animal data suggest that the platination level of blood proteins may be used as a measure of Pt concentration in tissue DNA.

Animals↗
PubMed1988

Determination of cisplatin in blood compartments of cancer patients.

A new approach has been developed to determine the levels of cisplatin in different blood compartments of treated cancer patients. The cisplatin content of plasma, plasma proteins, red blood cells and white blood cell DNA can be measured by atomic absorption spectroscopy (AAS). The approximate levels of cisplatin were 10, 500 and 100 ng Pt/ml blood in plasma, plasma proteins and haemoglobin, respectively; in white blood cell DNA, the level of cisplatin was about 1 pg/microgram DNA. Preliminary data indicate that cancer patients have measurable amounts of cisplatin in their blood compartments. Furthermore, antibodies have been raised against cisplatin-DNA, with which 50% inhibition occurs at 50-100 fmol cisplatin. The detection limit is about 1-10 fmol cisplatin/microgram DNA. Enzyme immunoassay techniques will be used to detect cisplatin-DNA adducts in white blood cell DNA of cancer patients.

Cisplatin↗
PubMed1986

DNA adducts in experimental cancer research.

The role of DNA adducts in the initiation of cancer is scrutinized in this presentation. Work on the activation of oncogenes, particularly on ras, has provided new evidence to link DNA adducts and tumour formation. Polycyclic hydrocarbons and nitroso compounds can cause activation of ras oncogenes through a defined point mutation. The properties of two DNA binding agents, styrene oxide and cisplatin are discussed. Styrene oxide is a versatile electrophile causing numerous adducts; cisplatin has a high specificity towards guanine-N-7 and cross-link formation. Finally, the relation of specific adducts to carcinogenic potency as defined by TD50 values is investigated. For small alkyl groups, O-alkylation of bases correlates with potency but among others, particularly the bulky carcinogens, 7-alkylguanines appear as correlates of potency. Most such potent agents forming 7-alkylguanines induce depurination and imidazole ring-opening.

Alkylation↗
PubMed1986

Effects of phenoxyacetic acids on the induction of chromosome aberrations in vitro and in vivo.

The effects of phenoxyacetic acid herbicides were investigated on the induction of chromosome aberrations in human peripheral lymphocyte cultures in vitro and in lymphocytes of exposed workers in vivo. Pure 2,4-dichlorophenoxyacetic acid (2,4-D; 0.125, 0.150, 0.200 and 0.350 mM) did not increase the number of aberrations, whereas the commercial 2,4-D formulation (0.125, 0.250, 0.500, 1.000 and 1.250 mM, with respect to phenoxyacetic acid concentration) significantly increased the number of chromosome aberrations in vitro (without exogenous metabolic activation). The phenoxy acid levels in the breathing zone of the workers varied between 0.3 and 0.4 mg/m3, and the concentrations of phenoxyacetic acids in the urine of the workers after exposure varied from 0.000 to 0.055 mmol/l. There were no increases in chromosome aberrations in peripheral lymphocytes of the exposed subjects.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1985

Radioactivity of size fractionated fly-ash emissions from a peat- and oil-fired power plant.

Concentrations of gamma-emitting natural radionuclides and 137Cs were analyzed in the size fractionated fly-ash emissions from a 100-MWt peat- and oil-fired power plant. The emitted fly ash was separated into five size fractions with a high-volume impactor with cut sizes of 1.3 micron, 2.1 micron, 4.2 micron and 10 micron. The greatest activity emissions were associated with the smallest size fraction, below 1.3 micron. The mass median aerodynamic diameter (MMAD) of the fly-ash particles after the electrostatic precipitator was 1.9 micron with a geometric standard deviation of 3.0 and the median of the 32 fly-ash emission samples was 8.73 mg MJ-1 with a geometric standard deviation of 1.3. Lead-210 gave the greatest particulate activity emission per input fuel energy, 18.7 mBq MJ-1, and showed a strong enrichment onto small fly-ash particles.

Carbon↗
PubMed1984

Natural radioactivity in and radon exhalation from Finnish building materials.

A total of 369 samples of Finnish building materials were tested for their 226Ra, 232Th and 40K concentrations. The rate of radon exhalation was measured from 19 samples of material and 34 dwellings were tested for their room air ventilation rate and radon concentration. The mean values of 226Ra, 232Th and 40K concentrations in ballast materials for concrete production were 34.2 Bq X kg-1, 39.0 Bq X kg-1 and 964 Bq X kg-1, with standard deviations of 18.7 Bq X kg-1, 19.5 Bq X kg-1 and 265 Bq X kg-1, respectively. The activity concentrations were higher in clay bricks than in concrete, the mean values being 79.8 Bq X kg-1, 61.6 Bq X kg-1 and 986 Bq X kg-1 for 226Ra, 232Th and 40K, respectively. The normalized radon exhalation rates from 15-cm-thick concrete, slag-aggregate concrete and by-product gypsum were 0.38 (Bq X m-2 X h-1)/(Bq X kg-1), 0.15 (Bq X m-2 X h-1)/(Bq X kg-1), and 0.06 (Bq X m-2 X h-1)/(Bq X kg-1), respectively. The ventilation rates in dwellings varied between 0.27 and 1.99 air changes per h, the mean value being 0.60 h-1, and the corresponding steady state radon concentrations in room air varied from 17.0 to 149 Bq X m-3 in blocks of flats made of concrete and from 11.2 to 61.9 Bq X m-3 in blocks of flats made of brick.

Air Pollutants, Radioactive↗
PubMed1978

Retrolental fibroplasia. Cases seen at the Helsinki University Eye Hospital 1956-1974.

In the period 1956-1974, 31 new cases of retrolental fibroplasia (RLF) were diagnosed at the Helsinki University Eye Hospital. All were alive in 1974. 90% weighed less than 1500 g at birth and the gestational age of less than 30 weeks at birth was present in 85%. All patients had required supplementary oxygen during the first weeks of life. 84% of the eyes had visual acuity of finger counting 1 m or less and when classified according to the corrected visual acuity in the better eye, 71% of the patients were practically blind according to the classification by Rintelen. 81% of the eyes showed one of the cicatricial stages of RLF, III to V, and 45% showed the grade V of the disease. 11% of the eyes showed corneal opacities, 44% a flat or absent anterior chamber, 11% had intraocular pressure of greater than or equal to 30 mmHg and 21% showed lenticular opacities. When the period of the observation was surveyed, it was found that during the latter half of the observation period, twice as many new cases of RLF were born. At a rough estimate it was calculated that in 1956-1974 at least 50 new cases of RLF developed in Finland.

Birth Weight↗