DNA solution(R) in cigarette filters reduces polycyclic aromatic hydrocarbon (PAH) levels in mainstream tobacco smoke.

Tobacco consumption represents a major health hazard to humans and, despite anti-smoking campaigns, the number of smokers remains high; thus the reduction of toxic compounds from tobacco smoke may reduce the health hazards of smoking. In the last 25 years cigarette manufacturers have introduced a variety of filter designs to reduce toxic and carcinogenic substances in tobacco smoke (normal filters, NF). However, large quantities of harmful constituents are inefficiently retained by commonly used cigarette filters. Following a patented method we modified commercial cigarette filters (modified filter, MF) by injecting a DNA solution into the filter tips; we then evaluated the reduced polycyclic aromatic hydrocarbon (PAH) levels in mainstream tobacco smoke of MF relative to NF. The PAH measured were: fluoranthene (FLUO), pyrene (PY), benzo(a)anthracene (B(a)A), chrysene (CRY), benzo(a)pyrene (B(a)P), benzo(b)fluoranthene (B(b)F), benzo(k)fluoranthene (B(k)F), benzo(g,h,i)perylene (BGP), dibenzo(a,h)anthracene (DBA). The levels of PAH in cigarette smoke after MF were significantly reduced (P<0.001) compared to NF, using a variety of cigarette brands in a smoking machine (44.5%+/-8.4 % and 41.8%+/-5% for total and carcinogenic PAH, respectively, means+/-SE). Using B(a)P(TEF) values the reduction in PAH concentrations were similar for all cigarette brands with the exception of Camel, where the reduction was lower considering B(a)P(TEF) values. Amongst carcinogenic PAH, B(a)A, B(b)F and B(k)F) were reduced by 50-58%, CRY, B(a)P and DBA by about 40%. In conclusion MF filters treated with DNA have the potential of decreasing the exposure to PAH in cigarette smoke. Since, unlike some previously proposed biological filters MF do not retain additional nicotine, the main addictive compound of tobacco smoke, these filters may not induce increased smoking to compensate for the reduction in the nicotine delivery to smokers.

High levels of carcinogenic polycyclic aromatic hydrocarbons (PAH) in 20 brands of Chinese cigarettes.

Tar and nicotine levels have been made to conform to EU standards as of 1 July 2004, but data on tobacco-derived carcinogenic compounds, such as PAH, in Chinese cigarettes are lacking in the literature. Levels of tar, nicotine, carbon monoxide and PAH were measured in 20 cigarette brands purchased in China between 2003 and 2004. Higher nicotine and tar levels were found in Chinese cigarettes than in European brands just 3 months before the above deadline; carcinogenic PAH levels were about 1.5 fold higher than in European cigarettes, but analysed singly, the mean value of benzo(a)pyrene (B(a)P) and dibenzo(a,h)anthracene (DBA), the most potent carcinogenic PAH yields, were 2.4 and 4.4 fold higher, respectively. Tar levels were well correlated with carcinogenic PAH (r = 0.53, P < 0.01), thus providing an easily measurable parameter for ranking various cigarette brands in developing countries where more sophisticated techniques might not be feasible for lack of funds and expertise.

Plant phenolic 4-coumaric acid protects against intestinal inflammation in rats.

BACKGROUND: Many plants contain significant amounts of 4-coumaric acid (4CA), a compound with antioxidant properties in vitro and in vivo. The aim of this study was to assess the effects of 4CA pretreatment on DNA oxidative stress induced by intestinal inflammation in rodents. METHODS: 4CA (50 mg/kg) was administered to rats for 14 days mixed in the diet. Colitis was induced on days 13 and 14 by administering 6% (w/v) dextran sodium sulphate (DSS) in the drinking water. RESULTS: In the colon mucosa, DSS treatment increased myeloperoxidase activity (P < 0.05), oxidative DNA damage (P < 0.01), and cyclooxygenase-2 (COX-2) expression (P < 0.01) and reduced superoxide dismutase-2 (SOD-2) expression (P < 0.05). It was found that treatment with 4CA prior to DSS-induced inflammation reduced oxidative DNA damage (P < 0.01), COX-2 over-expression (P < 0.01) and restored SOD-2 gene expression to control levels. Similar effects were observed with nimesulide administered p.o. (5 mg/kg, 1 day before and during DSS treatment). PGE levels in plasma and colon mucosa were increased by DSS treatment and this effect was inhibited by pretreatment with 4-CA (P < 0.01). CONCLUSIONS: Mild acute intestinal inflammation induced by DSS can be inhibited by 4-CA and this action is associated with the suppression of COX-2 expression and activity.

Sidestream tobacco smoke as the main predictor of exposure to polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) were measured in mainstream and sidestream tobacco smoke from 14 commercial brands of cigarettes purchased in Italy during 2001-2002. The PAHs detected in smoke and analysed with HPLC and a fluorimetric detector were: fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[a]pyrene, benzo[b] fluoranthene, benzo[k] fluoranthene, benzo[g,h,i]perylene and dibenzo[a,h]anthracene. The PAH levels in mainstream smoke from different cigarette brands obtained using an official smoking machine varied by about threefold (from 118 to 374 ng per cigarette for total PAHs and from 23.5 to 100 ng per cigarette for carcinogenic PAHs). Total PAH levels in mainstream smoke were correlated with tar content (r = 0.615, P < 0.05, n = 14). Total PAH content in sidestream smoke, measured by collection of all the smoke produced by a lit cigarette in a glass chamber, was about tenfold higher compared with mainstream smoke. The PAH content in sidestream smoke was relatively uniform (2.3-3.9 and 0.49-1.21 micro g per cigarette for total and carcinogenic PAHs, respectively) and was not correlated with tar content. These results indicate that cigarette manufacturing and filter characteristics influence the PAH composition of mainstream smoke, but have no effect on the PAH content in sidestream smoke, which is the main determinant of smokers' and non-smokers' exposure to PAHs in environmental tobacco smoke.

Polycyclic aromatic hydrocarbons air levels in Florence, Italy, and their correlation with other air pollutants.

Benzo(a)pyrene [B(a)P] air levels were measured in Florence (Italy) in the period 1992-2001. For the period 1999-2000 seven polycyclic aromatic hydrocarbons (PAH) (benzo(a)anthracene, crysene, benzo(a)pyrene (B(a)P), benzo(b)fluoranthene (B(b)F), benzo(k)fluoranthene, dibenzo(a,h)anthracene (DBA) and benzo(g,h,i)perylene (BGP)), were measured in the air in four different sites (one with heavy traffic (A), one in a park (B), one in a residential area (C) and one in a hill area (D)). B(a)P levels were elevated in 1992-1998 (maximum average value of winter months: 5.8 ng/ m3) but a decreasing trend was observed in the following years, probably due to improvement in vehicle emissions. The sum of PAH in the air in the period 1999-2000 was about one order of magnitude lower in the hill site (D) relative to the urban sites, and residential areas (B and C) had values 2.5-3 times lower compared to site A with a heavy traffic. PAH concentrations decreased in the warmer seasons of 2000 in all sites. A negative correlation was found between PAH levels and ozone. A positive correlation with carbon monoxide (CO) (r = 0.862, P < 0.001) and low B(a)P/BGP ratios, ranging from 0.44 to 0.51, indicated that vehicular traffic was the major PAH source in all monitored sites. Using B(a)P(TEF) values (toxic equivalency factors) for evaluating the biological activity of PAH, we found that the highest PAH contributors in terms of potential air carcinogenic activity were B(a)P and DBA. Therefore, in addition to B(a)P, DBA concentration should be considered in the evaluation of air quality in terms of PAH contamination.

Microsatellite instability in a population of sporadic colorectal cancers: correlation between genetic and pathological profiles.

BACKGROUND: Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear. AIMS: To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours. METHODS: Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed. RESULTS: High frequency microsatellite instability and low-frequency microsatellite instability and apparently stable cancers were different in terms of tumour localisation (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's-like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's-like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite instability tumours were preferentially located in the right colon and exhibited a higher frequency of loss of heterozygosity at the FHIT locus compared with low-frequency microsatellite instability and apparently stable cases (p=0.0243). Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer growth (p=0.0374), were the only factors affecting patient survival. However, a borderline improvement was noted in overall survival in high-frequency microsatellite instability and low-frequency microsatellite instability cancer patients (p=0.062). CONCLUSIONS: These results indicate that low-frequency microsatellite instability tumours have different genetics and histological features and suggest that they are a distinct group of colorectal cancers.

Mutations of the APC gene in human sporadic colorectal cancers.

BACKGROUND: Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis. METHODS: Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region. RESULTS: Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C). CONCLUSIONS: These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.

Effect of natural phenolic acids on DNA oxidation in vitro.

We examined the antioxidant activity of the following natural phenolic compounds present in food: 3-OH-benzoic acid (3-OH-BA); 4-OH-benzoic acid (4-OH-BA); 2,3-dihydroxybenzoic acid (2,3-diOH-BA); 3,4-dihydroxybenzoic acid (3,4-diOH-BA or protocatechuic acid); ferulic acid; caffeic acid; and 2-coumaric, 3-coumaric and 4-coumaric acids. We measured the inhibitory effect of these compounds on iron-dependent oxidative DNA damage in vitro [incubating herring sperm DNA with Fe(III)/GSH] or using cumene hydroperoxide (CumOOH) as a free-radical generating system; we also studied the interaction of these phenols with Fe(II) or Fe(III) spectrophotometrically. Among the tested compounds, 2,3-diOH-BA, 3,4-diOH-BA and caffeic acid interacted with Fe(II) and showed a potent inhibitory effect on iron-induced oxidative DNA damage. CumOOH-induced DNA oxidation was not modified by these compounds. On the contrary, 2-coumaric, 3-coumaric and 4-coumaric acids did not interact with iron but protected against oxidative DNA damage induced by Fe(III)/GSH and by CumOOH, indicating a direct free-radical scavenging activity of these compounds in both systems. The IC(50)+/-S.E.M. of the three coumaric acids against CumOOH-induced DNA oxidation was 44.2+/-2.0, 54.7+/-2.0 and 33.1+/-1.0 microM, respectively. On the contrary, 3-OH-BA and 4-OH-BA did not have scavenging activity and 3-OH-BA actually enhanced oxidative DNA damage. In conclusion, some natural phenolic acids, commonly present in food, have interesting protective activity against DNA oxidation in vitro and deserve further consideration as effective antioxidants in vivo.

Antioxidant and radical scavenging properties in vitro of polyphenolic extracts from red wine.

BACKGROUND & AIMS: Red wine polyphenols inhibit chemically-induced oxidative DNA damage in vivo in experimental animals through a mechanism which is still unclear. On this basis, we tried to clarify the mechanisms of inhibition of DNA oxidation in vitro by wine extracts containing monomeric and polymeric phenols (WE) and monomer-free complex polyphenols and tannins (WCPT) from red wine. METHODS: Oxidative DNA damage was induced by incubating DNA with GSH/Fe3+ or cumene hydroperoxide (CumOOH) in vitro and using 8-OH-2-deoxyguanosine (8-OHdG) levels as a measure of DNA oxidation. Levels of 8-OHdG were determined by HPLC coupled with electrochemical detector (ESA). RESULTS AND CONCLUSIONS: WCPT and WE, at microM concentrations, reduced concentration-dependently oxidative DNA damage induced by GSH/Fe3+. WCPT and WE also reduced DNA oxidation by CumOOH. In conclusion, complex polyphenols and tannin extracts from red wine, with or without small molecular phenols, prevent oxidative DNA damage through a dual mechanism, iron binding and direct free radical scavenging.

Determination of the levels of aromatic amines in indoor and outdoor air in Italy.

We studied the concentration of 10 primary aromatic amines (AA), which are classified as suspected carcinogens, in indoor and outdoor air in Italy. The measured AA included: aniline, o-toluidine, m-toluidine, p-toluidine, 2,3-dimethylaniline, 2,4-dimethylaniline, 2,5-dimethylaniline, 2,6-dimethylaniline, 2-naphtylamine and 4-aminobiphenyl. In the indoor environment (homes, offices and public buildings) the level of contamination (expressed as sum of 9 AA, excluding aniline) varied from 3 ng/m3 (hospital ward) to 207 ng/m3 (discotheque). In most indoor environments with no contamination from cigarette smoke the AA levels were below 20 ng/m3, whereas in the presence of smokers higher values were observed. Aniline levels were more erratic (varying from 53 ng/m3 (office of non-smokers) to 1929 ng/m3 (discotheque) and were not related to cigarette smoke. The concentration range of AA (excluding aniline) in the outside air varied from 3 ng/m3 (Siena) to 104 ng/m3 (Brindisi); aniline concentration was extremely variable. Most samples of outdoor air had AA levels lower than 40 ng/m3. In conclusion, AA are widespread air contaminants and attain a high concentration in heavily contaminated indoor environments, due to smoking and poor ventilation. AA occasionally attain a high level in outdoor air as well. Therefore, a strategy of reduction of the exposure to AA should consider the abatement of multiple sources of contamination.

Slow-release pellets of sodium butyrate do not modify azoxymethane (AOM)-induced intestinal carcinogenesis in F344 rats.

Butyrate exerts anti-tumour effects in vitro, but not consistently in vivo. We previously demonstrated that the administration of slow-release gastro-resistant pellets of sodium butyrate increases apoptosis in the colon mucosa of rats, an effect which may protect against carcinogenesis. Therefore, we studied whether the administration of butyrate pellets could protect rats against experimental colon carcinogenesis. Four to 5 week old male F344 rats were fed a high-fat (HF) diet (230 g/kg corn oil w/w) and treated s.c. with two injections (one week apart) of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight or saline. Rats were then divided into two groups: one group received sodium butyrate pellets mixed into the diet (1.5% w/w) for 33 weeks (150 mg butyrate/day) and the second group received the high-fat diet with no butyrate. Administration of sodium butyrate pellets in the diet did not significantly affect colon carcinogenesis: the number of intestinal tumours/rat was 1.6 +/- 0.2 in controls and 2.1 +/- 0.2 in butyrate-fed rats (means +/- SE; P = 0.22, by ANOVA), while the incidence of intestinal tumours was 79 (23/29) and 90% (27/30) in controls and in butyrate-fed rats, respectively (P = 0.29 by Fisher's exact test). The level of apoptosis in the tumours was not affected by butyrate, nor was the expression of p21(CIP), a cell cycle-related protein. In conclusion, the current study indicates that butyrate does not protect against AOM-induced colon carcinogenesis in rats.

Effect of simple phenolic compounds on azoxymethane-induced aberrant crypt foci in rat colon.

Because complex mixtures of plant polyphenols exert anticancer activity in animal models, we investigated whether low-molecular-weight natural phenolic compounds (2-OH-coumaric acid, 3-OH-coumaric acid, 4-OH-coumaric acid, 3-OH-flavone, 7-OH-flavone, 4-OH-benzoic acid, 3-OH-benzoic acid, and 2,3-OH-benzoic acid) affect azoxymethane (AOM)-induced aberrant crypt foci (ACF), which have been suggested to represent preneoplastic lesions, in the colon of rats. Male Fischer 344 rats were fed diets supplemented with 0.1% (wt/wt) of the different phenolic compounds, and after 2 wk they were treated twice (1 wk apart) with AOM (15 mg/kg s.c.); the dietary treatment continued until sacrifice, 7 wk after the first injection with AOM. The results showed that none of these phenolic compounds exerted chemopreventive activity on the ACF assay. On the contrary, 3-OH-flavone slightly, although significantly, increased (P < 0.05), the number of ACF per colon [157 +/- 7 and 198 +/- 14 (SE) in control and 3-OH-flavone groups, respectively, n = 10]. We also found that the number of "large" ACF was significantly increased in the group treated with 4-OH-benzoic acid. In conclusion, none of the phenolic compounds tested demonstrated a suppressive action on ACF induction by AOM.

Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo.

BACKGROUND: Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities. AIM OF THE STUDY: In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative damage in the rat colon mucosa. METHODS: Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.2 mg/kg/d) or thearubigin (40 mg/kg/d) by oral gavage. Colonocyte oxidative DNA damage was analysed at the single cell level using a modification of the comet assay technique. RESULTS: The results show that wine complex polyphenols and tannins induce a significant decrease (-62% for pyrimidine and -57% for purine oxidation) in basal DNA oxidative damage in colon mucosal cells without affecting the basal level of single-strand breaks. On the other hand, tea polyphenols, namely a crude extract of thearubigin, did not affect either strand breaks or pyrimidine oxidation in colon mucosal cells. CONCLUSIONS: Our experiments are the first demonstration that dietary polyphenols can modulate in vivo oxidative damage in the gastrointestinal tract of rodents. These data support the hypothesis that dietary polyphenols might have both a protective and a therapeutic potential in oxidative damage-related pathologies.

Effects of black tea, green tea and wine extracts on intestinal carcinogenesis induced by azoxymethane in F344 rats.

We investigated whether polyphenolic extracts from black tea, green tea or red wine affect azoxymethane (AOM)-induced intestinal carcinogenesis. Male F344 rats were treated 10 times (1 week apart) with AOM (7.4 mg/kg, s.c.) and then allocated into groups receiving black tea, green tea or red wine extracts mixed in the diet at a dose of 50 mg/kg body weight for 16 weeks. In the rats treated with black tea or wine extracts, there were significantly fewer colorectal tumours than in controls (the mean +/- SE number of tumours/rat was 2.54 +/- 1.6 in controls, 1.54 +/- 1.4 in the black tea group, 3.2 +/- 1.9 in the green tea group and 1.63 +/- 1.6 in the wine extract group). Significantly fewer rats in the black tea and wine extract groups had adenomas than in controls (86%, 59%, 90% and 50% of rats in the control, black tea, green tea and wine extract groups, respectively, had adenomas). The tumours from the black tea group and, to a lesser extent, those from the wine group, had a significantly greater apoptotic index than tumours in controls (mean +/- SE apoptotic index: 2.92 +/- 0.25, 4.13 +/- 0.46, 2.88 +/- 0.30 and 3.72 +/- 0.46 in controls, black tea, green tea or wine extract groups, respectively). In contrast, the apoptotic index of the normal mucosa did not vary among groups. These data indicate that black tea and wine extracts, but not green tea extracts, can protect against AOM-induced colon carcinogenesis by a mechanism probably involving increased apoptosis in tumours.

Inhibition of 1,2-dimethylhydrazine-induced oxidative DNA damage in rat colon mucosa by black tea complex polyphenols.

The effect of black tea polyphenols on 1,2-dimethylhydrazine (DMH)-induced oxidative DNA damage in rat colon mucosa has been investigated. Fischer 344 rats were treated orally with thearubigin (TR) or theafulvin (TFu) for 10 days (40 mg/kg), injected ip with DMH (20 mg/kg) or saline and sacrificed 24 hr after DMH administration. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in colonic mucosa DNA and expressed as a ratio relative to 2'-deoxyguanosine (2dG). Control rat mucosa had 8-OHdG values of 1.12 +/- 0.14/10(5) dG (mean +/- SEM, n=11), whereas DMH-treated rats significantly higher values (1.52 +/- 0.14/10(5) dG, n=26, P<0.05). Pretreatment of rats with TR had significantly inhibited DMH-induced oxidative DNA damage 0.99 +/- 0.09/10(5) dG, n=10, P<0.05) and a similar, although less marked, effect was observed with TFu (1.15 +/- 0.19/10(5), n=9, P=0.06). These findings confirm that DMH causes oxidative DNA damage in the colon mucosa of rats and demonstrate that this effect is prevented by the consumption of complex polyphenols from black tea.

Detection of somatic DNA alterations in azoxymethane-induced F344 rat colon tumors by random amplified polymorphic DNA analysis.

Colon carcinogenesis induced in rats by azoxymethane (AOM) is a useful experimental model as it mimics the human adenoma-carcinoma sequence and allows the study of dietary variation and of the effects of chemopreventive substances. Alterations of specific oncogenes and tumor suppressor genes (APC and K-ras) play roles at different stages of this carcinogenesis process. Recently, it has been suggested that genomic instability is the necessary step for the generation of multiple mutations underlying the occurrence of cancer. We studied the frequency of K-ras and microsatellite instability (MSI) in 30 colorectal tumors induced by AOM (30 mg/kg) in F344 rats. We also used the random amplified polymorphic DNA (RAPD) method to identify genomic alterations in chemically induced aberrant crypt foci (ACF), adenomas and adenocarcinomas. K-ras mutations were identified in 16.7% of the cases (5/30; 9% in adenomas and 37.5% in adenocarcinomas) and MSI in 20% (6/30) of the tumors (only one sample exhibited instability at more than one locus). Of 21 primers used for the RAPD assay, six were very informative. All the analyzed tumors (16/16) showed at least one RAPD profile with lost or additional bands compared with the normal mucosa. A lower level of genomic alteration was present in the ACF analyzed (7/10). In conclusion, K-ras and MSI are not often involved in the AOM carcinogenesis in the rat, whereas extensive genomic instability is always present and can be detected using the RAPD analysis.

Clinicopathologic features and FHIT gene expression in sporadic colorectal adenocarcinomas.

BACKGROUND: The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas. METHODS: FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene. RESULTS: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours. CONCLUSIONS: Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.

[Levels of polycyclic aromatic hydrocarbons (PAHs) in air samples in the city of Arezzo (1997-1998)]. / Livelli aerei di idrocarburi policiclici aromatici (IPA) nella città di Arezzo (1997-1998).

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environment pollutants of air, water and soil. Since many PAHs are potent mutagens and/or carcinogens the occurrence of these compounds in the lower atmosphere is an important element of environmental pollution. We measured PAH levels in airborne particles collected in the town of Arezzo, (Tuscany, Italy), during the period April 1997-February 1998. Air monitoring for 24 h was repeated for 7 days, during two weeks, in each season; a total of 84 air samples were obtained sampling two urban sites where the traffic is the main source of pollution. One site is a residential area. The data of this study indicate a pronounced seasonal variation in PAH levels and show that in cold spells other sources of contamination besides vehicular traffic are important.

Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh.

We extracted, purified and characterized 8 sesquiterpene fractions from Commyphora molmol. In particular, we focused our attention on a mixture of furanodiene-6-one and methoxyfuranoguaia-9-ene-8-one, which showed antibacterial and antifungal activity against standard pathogenic strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, with minimum inhibitory concentrations ranging from 0.18 to 2.8 micrograms/ml. These compounds also had local anaesthetic activity, blocking the inward sodium current of excitable mammalian membranes.