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Biomedical subjects

R Albanese

Publications and source records attributed to R Albanese.

10 recordsLinked to original sources

[Surgical treatment of unrepairable vesicovaginal fistulas].

The authors discuss different types of urinary diversion as the therapy of unrepairable vesico-vaginal fistulas. They also describe the therapy performed in their experience and underline that, at the moment, rectal bladder is to be considered the best solution.

Colon

Mutagenicity to bacteria, cultured cells, and rodents of the human carcinogen chlornaphazine.

The human carcinogen and nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic to Salmonella and, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels greater than 2.5 micrograms/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in corn oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoeisis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays.

Animals

Species-specific response to the rodent carcinogens 1,2-dimethylhydrazine and 1,2-dibromo-3-chloropropane in rodent bone-marrow micronucleus assays.

1,2-Dimethylhydrazine is confirmed as active in the mouse bone-marrow micronucleus assay when administered as an aqueous solution via oral gavage to three different strains of mice. It is also shown to be inactive in a corresponding rat assay under similar conditions of test. The observations were independently repeated in two laboratories. In contrast, 1,2-dibromo-3-chloropropane showed the reverse profile, being active in the rat bone-marrow assay but inactive in the mouse; the latter observations were also made in two laboratories. The carcinogen procarbazine was active in both species. These findings are discussed within the context of the present GeneTox revision of the standard test protocol of the rodent bone-marrow micronucleus assay.

1,2-Dimethylhydrazine

Chemically induced aneuploidy in female germ cells.

Female mice were dosed with the spindle poisons colcemid (5 mg/kg) or colchicine (2 mg/kg) or with a dihydropyridazinone (ICI 109,081; 5 mg/kg; which inhibits oocyte maturation) or with saline, the vehicle control. The dosed females (whose ovulation was synchronized using exogenous gonadotrophins) were mated with undosed males, 12 or 3 h prior to ovulation, coresponding to MI or MII stages in preovulatory oocytes. First-cleavage embryos derived from these matings were then analysed for numerical chromosome aberrations. There were no numerical aberrations in the embryos derived from control matings. Polyploid embryos were isolated from females dosed with colchicine. When females were dosed 3 h prior to ovulation (PO) 26% of the first-cleavage embryos were polyploid; in those dosed 12 h PO it was 100%. Colcemid and ICI 109,081 induced both polyploid and aneuploid embryos; with colcemid these aberrations were only observed in the embryos derived from oocytes of females dosed 3 h PO. At this sample time 4% of the embryos were polyploid and 24% were aneuploid. In contrast, the majority of aberrations induced by ICI 109,081 were observed in females dosed 12 h PO where 10% of the embryos were polyploid and 3% were aneuploid.

Aneuploidy

The assessment of micronucleated polychromatic erythrocytes in rat bone marrow. Technical and statistical considerations.

Traditionally, the mouse is the species of choice for the rodent bone marrow micronucleus assay (MN). However, the rat is used for most other toxicological studies. The suitability of the rat as a test species for the MN was therefore investigated. In this paper, the methodological aspects of the assay have been considered. The distribution and incidence of micronucleated polychromatic erythrocytes (MPEs) on bone marrow slides prepared by two techniques, the conventional smear and the paint-brush technique, were assessed in control and cyclophosphamide-dosed male and females rats. MPEs were shown to be homogeneously distributed when assessed over a large number of PEs on slides prepared by both techniques, but when viewed over a few hundred PEs (less than 500 PEs), the incidence of MPEs on the same slides was seen to vary considerably (0-10 MPEs/500 PEs). Variability was within acceptable limits when at least 1000 PEs/animal were analysed. The spontaneous incidence of MPEs in the AP rat is low (0-2 MPEs/1000 PEs). Cyclophosphamide increased the incidence markedly and there was a wide inter-animal variability in the response (10-40 MPEs/1000 PEs). The paint-brush technique is considered technically simpler and recommended over the smear technique. This study shows that MPEs can be accurately scored in the bone-marrow of the rate provided due consideration is given to staining and sample size of PEs analysed per animal.

Animals

Mammalian male germ cell cytogenetics.

The methods used for the detection of chemically induced chromosome damage in male germ cells are discussed. These tests have been divided into direct and indirect cytogenetic methods. The direct methods assess chromosome damage in the dosed animal but analysis is restricted to the dividing spermatogonia and spermatocytes. Using indirect methods, chromosome damage is assessed in the F1 progeny of the dosed male and analysis covers all germ cell stages. Both methods can provide evidence of germ cell exposure but the data obtained from the indirect tests are considered more relevant since a positive result clearly constitutes unequivocal evidence of transmitted damage. The analysis of one-cell embryos from matings involving dosed parents is considered to be the most useful indirect test system since both structural and numerical aberrations in male and female F1 offspring can be assessed. Although relevant to the assessment of mutagenic hazard, the technically demanding methods used in the germ cell techniques prevent their use for preliminary screening programmes.

Animals

Sodium fluoride and chromosome damage (in vitro human lymphocyte and in vivo micronucleus assays).

The clastogenic potential of sodium fluoride was determined both in vitro (using cultured human lymphocytes) and in vivo (using the rat bone-marrow micronucleus test). The incidence of chromosome aberrations in human lymphocyte cultures exposed to 20 or 40 micrograms/ml sodium fluoride (3 and 9% respectively) was significantly increased compared with control cultures (0.5%). However, the incidence of micronucleated polychromatic erythrocytes in male AP rats dosed 1000 mg/kg NaF (the maximum tolerated dose over 24 h) or 500 mg/kg NaF was similar to that in the animals dosed distilled water (vehicle control). Thus, sodium fluoride is clastogenic in vitro but not in vivo.

Cells, Cultured