Persistence of cytogenetic damage induced by alkylating antineoplastic drug phopurinum in human lymphocytes in vivo and in vitro.

Sister chromatid exchanges (SCEs) and structural chromosome aberrations (CAs) induced by cytostatic drug phopurinum in vivo and in vitro were studied in human lymphocytes. Phopurinum was found to cause a significant increase of CAs in lymphocytes of patients undergoing cytostatic therapy. Increased CA rates, however, declined rapidly after the cessation of treatment. This decline observed in vivo is in agreement with experimental results obtained in vitro, where it is found that the induction of SCEs and CAs occur only during the 1st cell cycle after pulse-treatment as G1 stage with phopurinum. Thus, phopurinum induced short-lived DNA damage both experimentally and in vivo.

In vitro interaction between two antineoplastic drugs--phopurinum and interferon alpha 2.

Induction of sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) by two antineoplastic drugs--phopurinum (2-dimethylamino-6-diethyleneiminophosphamido-7-methylpurine) and recombinant human interferon alpha 2 (rHuIFN-alpha 2) was studied in human lymphocytes in vitro. Phopurinum was found to cause a significant increase of both SCEs and CAs in lymphocytes, while rHuIFN-alpha 2 induced only SCEs. Combined treatment with these two drugs reduced SCE and CA levels as compared with those induced by phopurinum alone. The maximal extent of reduction, however, was observed at intermediate doses of phopurinum.

High titers of antibodies to two human polyomaviruses, JCV and BKV, correlate with increased frequency of chromosomal damage in human lymphocytes.

Associations of antibody titers to the JC and BK human polyoma viruses and the frequency of chromosome aberrations (CA) in human peripheral blood lymphocytes were studied. Study group consisted of 33 workers occupationally exposed to low doses of ionizing radiation and 11 control persons. There were no statistically significant differences in the JC and BK virus titer values between two groups of donors. It was found that JC and BK virus titers explained approximately 6% of total inter-individual variation in CA frequency. Such factors as alcohol abuse, age and, in this special group, exposure to ionizing radiation explained an additional 53% of the total variation in CA frequency. In six clean-up workers and one control, rogue cell (cells with multiple chromosome-type aberrations) were found. The incidence of rogue cells correlated significantly with JC and BK virus titers as well as a history of recent acute respiratory disease.

Cytogenetic analysis of children under long-term antibacterial therapy with nitroheterocyclic compound furagin.

Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients with urinary tract infections (UTIs). Children were exposed to diagnostic levels of X-rays during voiding cystourethrography and subsequently treated for one to 12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1-aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and structurally similar to well-known antibacterial compound nitrofurantoin. Increased frequencies of CAs were found in children undergoing voiding cystourethrography as compared with the unexposed, acentric fragments being the most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a significant decrease in the frequency of acentric fragments was determined with the time elapsed since X-ray examination was performed. A time-independent increase in SCE frequency was found in lymphocytes of children treated with furagin. Total CA frequency did not differ significantly between groups of children with various duration of furagin treatment. However, frequency of chromatid exchanges (triradials and quadriradials) increased significantly with duration of treatment.

Chromosomal aberrations and sister-chromatid exchanges in Lithuanian populations: effects of occupational and environmental exposures.

Cytogenetic analysis of chromosomal aberrations (CA) in 175,229 cells from 1113 individuals, both unexposed and occupationally or environmentally exposed to heavy metals (mercury and lead), organic (styrene, formaldehyde, phenol and benzo(a)pyrene) and inorganic (sulfur and nitrogen oxides, hydrogen and ammonium fluorides) volatile substances and/or ionizing radiation was performed. In addition, 11,250 cells from 225 individuals were scored for the frequency of sister-chromatid exchanges (SCE). Increased frequencies of CA were found in all occupationally exposed groups. A principal difference between the exposure to heavy metals and organic substances was found: increase in the CA frequency was dependent on duration of exposure to mercury but not dependent on duration of exposure to styrene, formaldehyde and phenol. A higher CA incidence was found in lymphocytes of children living in the vicinity of a plant manufacturing phosphate fertilizers. This indicates that children are a sensitive study group for the assessment of environmental exposure. However, the results of SCE analysis in these children were inconclusive. Exposure to ionizing radiation was found to cause chromosome breaks and chromatid exchanges in Chernobyl clean-up workers and chromatid breaks, chromatid exchanges, dicentric chromosomes and chromosome translocations in workers from the Ignalina Nuclear Power Plant. The increased frequency of chromatid exchanges in individuals exposed to ionizing radiation was quite unexpected. This may be attributed to the action of some unrecognized life-style or occupational factors, or to be a result of radiation-induced genomic instability. Also an increased SCE frequency was found in lymphocytes of Chernobyl clean-up workers.

Genotoxicity of dill (Anethum graveolens L.), peppermint (Menthaxpiperita L.) and pine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila melanogaster.

Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and seeds, peppermint (Menthaxpiperita L.) herb and pine (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo. In the CA test, the most active essential oil was from dill seeds, then followed essential oils from dill herb, peppermint herb and pine needles, respectively. In the SCE test, the most active essential oils were from dill herb and seeds followed by essential oils from pine needles and peppermint herb. Essential oils from dill herb and seeds and pine needles induced CA and SCE in a clear dose-dependent manner, while peppermint essential oil induced SCE in a dose-independent manner. All essential oils were cytotoxic for human lymphocytes. In the SMART test, a dose-dependent increase in mutation frequency was observed for essential oils from pine and dill herb. Peppermint essential oil induced mutations in a dose-independent manner. Essential oil from dill seeds was almost inactive in the SMART test.

Cytogenetic monitoring of nuclear workers occupationally exposed to ionising radiation.

Chromosome aberration (CA) analysis using Giemsa techniques was performed in blood lymphocytes of 84 nuclear workers with cumulative doses of 1-632 mSv during employment periods of 1-25 y. The control group comprised 82 healthy male donors. An estimated CA frequency in the total radiation-exposed group was significantly higher when compared with the controls (2.27 vs. 1.76 CA/100 cells, p < 0.05). CA analyses revealed no significant differences between workers with external gamma radiation exposure and the controls (1.60 vs. 1.76 CA/100 cells, p > 0.05). However, significant increase in the total CA frequency was determined in workers with additional internal exposure (2.54 CA/100 cells, p < 0.05) and those with registered neutron doses (2.95 CA/100 cells, p < 0.01). No correlation was found between CA frequency and occupational exposure dose. Borderline significant correlation was found between duration of employment and total CA (r = 0.218, p = 0.046, Fig. 2) and chromosome-type aberration (r = 0.265, p = 0.015) frequency.

Cytogenetic analysis of peripheral blood lymphocytes of children treated with nitrofurantoin for recurrent urinary tract infection.

The objective of this study was to determine whether nitrofurantoin, used for long-term antimicrobial prophylaxis of urinary tract infection, may induce chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) in lymphocytes of treated children. Ninety-nine blood samples were taken from 69 children aged from 0.2 to 13 years and suffering from urinary tract infection. The treatment consisted of oral administration of nitrofurantoin at doses of 5-8 mg/kg/day for the first 7 days and at doses of 1-2 mg/kg/day for the rest of the treatment period. Blood was sampled before the start of the nitrofurantoin therapy and after 1, 3, 6 and 12 months of the therapy. Analysis of variance showed no statistically significant increase in CA and SCE frequencies in lymphocytes of children treated with nitrofurantoin for 1-12 months. However, a significant increase in SCE rates was determined in lymphocytes of those patients whose blood samples were available both before and after treatment with nitrofurantoin (6.21 +/- 0.28 and 7.30 +/- 0.39 SCE/cell, respectively, P = 0.0315, Student's paired t-test). Moreover, there was a statistically significant correlation (r = 0.6603, P = 0.0270) between cumulative dose of nitrofurantoin and SCE frequency in lymphocytes of children after 1 month of the therapy. Also, in vitro experiments indicated that nitrofurantoin was able to induce both CAs and SCEs in human lymphocytes. Positive findings with chromosome aberrations and SCEs in vitro and suggestive results with SCEs in vivo indicate that further, much larger follow-up studies are needed to elucidate the genetic safety of the therapeutic use of nitrofurantoin.