Cytoplasmic DNA from petite colonies of Saccharomyces cerevisiae: a hypothesis on the nature of the mutation.

The density of the cytoplasmic DNA of two strains of "petite" mutants of yeast, obtained by treatment with acriflavin and with ultraviolet light, was examined in cesium chloride density-gradient centrifugation and in all cases appeared to be less than that of the wild type. A cytoplasmic respiratory-deficient strain, treated with additional acriflavin, can show a further shift of the position of the satellite band, always in the direction of reduction of density. Also, from the p(+) x p(-) cross, p(-) strains can be recovered in which the density of the satellite DNA is different from the density of the parent p(-) strain. This finding suggests the existence of recombination in cytoplasmic DNA moleciules.

Colony density influences invasive and filamentous growth in Saccharomyces cerevisiae.

The effect of colony density on the dimorphic switch was determined in natural strains of Saccharomyces cerevisiae. In some strains invasiveness and pseudohyphal (PH) growth were highly sensitive to colony density; moreover, strains constitutively able to invade the substrate with PH formation positively influenced the invasiveness but not the PH growth of a different strain less prone to the dimorphic switch.

Growth requirements and lipid metabolism of Pityrosporum orbiculare.

The yeast, Pityrosporum orbiculare, isolated from lesions from lesions of tinea versicolor, grows in vitro only if fatty acids from the C12 to C24 series are added to the culture medium. Except for elaidinic and nervonic acids, all saturated and unsaturated fatty acids tested support growth. P. orbiculare can synthesize various lipid fractions containing both saturated and unsaturated fatty acids from a single fatty acid. Glucose and asparagine stimulate growth but exogenous vitamins do not.

Effect of dicarboxylic acids on lentigo maligna.

Dicarboxylic acids from C8 to C14 are competitive inhibitors of tyrosinase in vitro, and here, the effect of a cream containing 15% azelaic acid (C9) on 3 cases of lentigo maligna is described. The lesions were treated for 90 days, with remarkable clinical and histological effect, maintained for up to 2 yr after cessation of treatment. Progress during treatment of one case was additionally monitored by electron microscopy, which revealed progressive elimination of abnormal melanocytes both basally and suprabasally, and their replacement by essentially normal cells engaged in normal melanogenesis. There was also progressive diminution in the general disorganization of the epidermis, and disappearance of lymphocyte response. It is concluded that dicarboxylic acids have a direct inhibitory and cytotoxic effect on abnormally active or structurally disordered melanocytes in lentigo maligna, but further investigations are required to establish their precise mode of action. Similar application of dicarboxylic acids to normal skin affects only a small proportion of melanocytes, suggesting that some phasic factor, or individual states of activity, may be concerned in their susceptibility.

Analysis of mitotic nondisjunction with Aspergillus nidulans.

Two methods to detect the induction of nondisjunction with a diploid stable strain of A. nidulans are described. The first method gives only qualitative results, while the second method is quantitative and dose-effect curves can be done. Some physiological parameters affecting the induction of nondisjunction can also be studied, because either quiescent or germinating conidia can be treated with the drug under test. Some agents inducing nondisjunction were also tested for the induction of point mutation and somatic crossing-over with these comparative analysis. Two classes of agents inducing nondisjunction may be detected: the first causes all possible types of genetic damage either on quiescent or germinating conidia (a representative of this class is MMS) and acts presumably on the DNA level; the second acts only on germinating conidia and does not produce point mutation or crossing over. A representative of this class is Benomyl which interferes with spindle microtubules. A list of compounds tests is included.

Malignant melanoma in Rome, Italy, 1970-9.

An epidemiological study was conducted in the city of Rome and the incidence of malignant melanoma was determined retrospectively for the years 1970-9. All patients had legal residence in Rome and a histological diagnosis of melanoma during that period; only cases of malignant melanoma of the skin (ICD 172, 8th revision) were considered. A total of 17 public and 82 private hospitals were involved in the study with 11 081 and 6127 hospital beds respectively. All the hospitals in the study had one of the following therapeutic and diagnostic facilities: internal medicine, dermatology, oncology, radiology, surgery, plastic surgery, histopathology. Analyses of incidence are based on 500 cases, 237 males and 263 females, collected in the period 1970-9. The data indicate a positive time trend in incidence; the average annual increase is 0.27 cases/year per 100 000. The data show that in a Mediterranean and Latin country such as Italy the incidence of melanoma presents the same ascending trend as that of other Caucasian countries, whether European or not, the slope of the curves is similar for both sexes. The distribution of the primary site for both sexes is closely parallel to that described for all Caucasian populations, the lower limbs being more affected in females and the trunk in males.

Mutagenicity of dichlorvos and other structurally related pesticides in Salmonella and Streptomyces.

The following pesticides: azinphosmethyl, diallate, dichlorvos, EPTC, fenchlorphos, mevinphos, monocrotophos, noruron, parathionmethyl, triallate, trichlorphon and vegadex were tested for the ability to induce his+ revertants in four histidines requiring strains of Salmonella typhimurium--TAI 535(missense), TAI 536, TAI 537 and TAI 538 (frame-shift)- and resistance to low levels of streptomycin in Streptomyces coelicolor. Dichlorvos, which is a phosphoric ester with a dichlorovinyl group as side chain, and trichlorphon, which is known for its spontaneous conversion in dichlorvos, are both mutagenic in Salmonella (strain TAI535) and Streptomyces. Five organophosphorus pesticides similar to dichlorvos but devoid of the vinyl group are not mutagenic. Three carbamates, diallate, triallate and vegadex, which contain a chloroallyl group similar to the vinyl group of dichlorvos are mutagenic in Streptomyes; triallate and vegadex are powerful mutagens also in Salmonella (strain TAI535); two other carbamates devoid of the chlorinated group are not mutagenic. The results suggest that the presence of a vinyl chloride or allyl chloride group in the molecule of these pesticides is responsible for the ability to induce point mutations in Salmonella and Streptomyces.

An uvsB mutant of Aspergillus nidulans with high variable spontaneous mutation and intergenic mitotic recombination frequencies.

An UV-sensitive mutant has been isolated with a new technique which allows isolation of UV-sensitive and UV-non-mutable mutants in Aspergillus nidulans. This mutant is an allele of the known uvsB gene but shows some features not previously described in the alleles so far isolated. Its more important characteristics are: (1) Frequency of mitotic intergenic recombination is strongly increased in uvs/uvs diploids and it is highly variable in different clones: it varies from a minimum of 40-fold to a maximum of about 1000-fold in comparison with uvs+/uvs+ strains. (2) The frequency of mitotic intergenic recombination is increased also in the heterozygous diploids. (3) The frequency of spontaneous mutation is higher and highly variable in different subclones: it may be increased up to 1000-fold.

Frequency of spontaneous and induced recessive mutations in a diploid strain of Aspergillus nidulans.

The spontaneous and UV-induced frequencies of recessive mutations have been studied in a diploid strain of Aspergillus nidulans, by the p-fluoro-phenylalanine (FPA) and 8-azaguanine (8-AZA) resistance tests, on either resting or germinating conidia. Observed frequencies are in the order of magnitude of those expected, which have been calculated considering the observed mutation frequencies in the haploid strain as well as the mitotic recombination frequencies. We also review some papers which claim to have found higher rates of recessive mutations in mammalian cell lines; in some cases no really higher rates are evident and the authors' conclusions often rest on misinterpretation of their own data.

The genetic activity of 6-N-hydroxylaminopurine in Aspergillus nidulans.

The activity of a base analog (6-N-hydroxylaminopurine, HAP) has been tested on Aspergillus nidulans. In germinating haploid conidia HAP is a strong mutagen, while it does not have any activity in resting conidia. Moreover, HAP does not increase the frequency of recombination in germinating conidia. The mutagenic activity of this base analog has also been tested in diploid conidia of A. nidulans; in fact, it has been shown (Pavlov et al., 1991) that the HAP-induced frequency of heteroallelic recessive mutations in diploid cells of the yeast S. cerevisiae is higher than expected. In A. nidulans, we did not observe any increase in the frequency of recessive homozygous fpaA/fpaA (p-fluorophenylalanine-resistant) mutants over the expected one, which has been calculated on the basis of the observed mutation frequency in the haploid strain.

A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans.

A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation.

Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans.

Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.

A comparative study on selected chemical carcinogens for chromosome malsegregation, mitotic crossing-over and forward mutation induction in Aspergillus nidulans.

10 "false negative" chemical carcinogens, i.e. ineffective in bacterial mutagenicity assays, were thoroughly investigated for their genotoxic activity in the mould Aspergillus nidulans. Forward mutations (methionine suppressors), mitotic crossing-over and chromosome malsegregation were the end-points scored. Positive results were obtained in tests for the induction of mitotic segregation with benzene, ethylenethiourea and urethane, which increased the frequency of abnormal presumptive aneuploid colonies with euploid sectors showing whole chromosome segregation (i.e. non-disjunctional diploids and haploids). The same compounds were ineffective in increasing the frequency of mitotic crossing-over or forward mutations. The other chemical carcinogens investigated, namely acetamide, amitrole, dieldrin, heptachlor epoxide, nitrilotriacetic acid, p,p'-DDT and thiourea were ineffective both as inducers of forward mutations and mitotic segregation.

A single-centre, before-after study of the short- and long-term efficacy of Narivent(®) in the treatment of nasal congestion.

OBJECTIVE: Nasal congestion is a common symptom in allergic and nonallergic rhinitis, rhinosinusitis and nasal polyposis. The present study evaluated the clinical effectiveness of Narivent(®), an osmotically-acting medical device with anti oedematous and anti-inflammatory effects, in nasal congestion. METHODS: A single-centre, prospective study with a pre- post design and consecutive patient enrolment was conducted in an Italian otolaryngology department. Patients with persistent nasal congestion were allocated to treatment groups as follows: group 1 (n = 36) treated for 7 days; group 2 (n = 56) treated for 30 days. In each group, patients received two puffs of Narivent(®) into each nostril twice daily. Symptom severity was assessed subjectively on a 0-10 visual analogue scale, and objectively by the presence/absence of signs and symptoms. Differences in subjective and objective severity measures before and after treatment were compared using Wilcoxon's signed rank test. RESULTS: All symptoms and objective scores improved after treatment with Narivent(®) for 7 or 30 days and no adverse effects were reported by the patients in either group. CONCLUSION: Narivent(®) appears to be efficacious in treating nasal congestion over a 7- or a 30-day period.