Cytotoxicity of isolated compounds from Picrasma crenata (Vell.) Engl. in animal tumor cell (HTC).

The study aim was to evaluate the cytotoxic activity, using the MTT test [3-(4,5-Dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide], from the crude extract of Picrasma crenata (Pau Tenente) and its isolated compounds, quassin and parain, in culture of rat liver tumor cells (HTC). The test was carried out exposing the cells for 24, 48 and 72 hours to concentrations of 5, 10, 50, 100, 200, 300, 400, 500 and 1000 µg of crude extract of Pau Tenente/mL of culture medium and 1, 5, 10, 15, 20, 40, 60, 80 and 100 µg of quassin or parain compounds/mL of culture medium. The absorbances averages results obtained showed that the crude extract did not present cytotoxicity for the HTC cells in all the concentrations and evaluated times. For quassin, the concentrations of 80 and 100 µg/mL were cytotoxic, after 72 hours of treatment. For parain, the concentrations of 1, 5, 20, 40, 60, 80 and 100 µg/mL, in 72 hours, were cytotoxic, revealing a new activity for this compound. Thus, the results demonstrate a first indication of the cytotoxic activity of compounds quassin and parain, adding an important social and economic value to them, and may have application in future research and in pharmaceutical industry.

Cytotoxicity of capsaicin and its analogs in vitro.

Capsaicin (CAP) is the main compound responsible for the spicy flavor of Capsicum plants. However, its application can be inhibited due to its pungency and toxicity. This study aimed to evaluate and compare the cytotoxic effect of CAP and its analogs N-benzylbutanamide (AN1), N-(3-methoxybenzyl) butanamide (AN2), N-(4-hydroxy-3-methoxybenzyl) butanamide (AN3), N-(4-hydroxy-3-methoxybenzyl) hexanamide (AN4) and N-(4-hydroxy-3-methoxybenzyl) tetradecanamide (AN5) on the hepatoma cells of Rattus norvegicus using the MTT test. The results showed cytotoxicity of CAP at concentrations of 100, 150, 175, and 200 µM (24 hours), AN1 at 150 and 175 µM (48 hours), AN2 at 50 µM (24 hours) and 10, 25, 50, and 75 µM (48 hours), AN4 at 175 µM (24 hours), and AN5 at 50 µM (48 hours). Removing the hydroxyl radical from the vanillyl group of capsaicin, together with reducing the acyl chain to 3 carbons, which is the case of AN2, resulted in the best biological activity. Increasing the carbon chain in the acyl group of the capsaicin molecule, which is the case of AN5, also showed evident cytotoxic effects. The present study proves that the chemical modifications of capsaicin changed its biological activity.

Cytotoxicity of extracts and compounds isolated from Croton echioides in animal tumor cell (HTC).

The search for compounds with anticancer effects is of paramount importance today due to the high incidence of the disease. The Euphorbiaceae family is known for having compounds with therapeutic properties, one of its genera being Croton. It has several species, which contain compounds already known for their biological activities, presenting anti-inflammatory, antimicrobial and anticancer properties. Thus, the cytotoxicity/antiproliferative activity of semi-purified fractions and compounds isolated from Croton echioides in liver tumor cells of Rattus norvegicus (HTC) was evaluated by the MTT test. The semi-purified fractions showed cytotoxicity at concentrations above 200 µg/mL, at 24, 48 and 72 hours, reaching cell viability of 24.78% [400 µg/mL] at 24 hours, 12.79% [500 µg/mL] at 48 hours and 10.57% [300 µg/mL] at 72 hours. For the isolated compounds, lupeol had a cytotoxic effect in all concentrations (1, 5, 10, 15, 20, 40, 60, 80 and 100 µg/mL) and tested times (24, 48 and 72 hours), reaching minimum viability of 4.37% [100 µg/mL], within 72 hours. The clerodan diterpenes CEH-1 and CEH-4 also showed antiproliferative activity, with minimum viability of 36.19% [100 µg/mL] over 72 hours and 21.33% [100 µg/mL] over 48 hours, respectively. However, the clerodan diterpenes CEH-2 and CEH-3 did not shows a cytotoxic effect for HTC cells. Thus, there is a cytotoxic/antiproliferative potential of C. echioides against tumor cells, with targeted to mitochondrial enzymes, associated with cell proliferation, indicating that this species deserves prominence in the search for new molecules for the treatment of cancer.

Cytotoxicity of iodine-131 radiopharmaceutical in tumor and non-tumor human cells and radioprotection by integral juices of Vitis labrusca L.

Iodine-131 (I-131) radioisotope it causes the formation of free radicals, which lead to the formation of cell lesions and the reduction of cell viability. Thus, the use of radioprotectors, especially those from natural sources, which reduce the effects of radiation to healthy tissues, while maintaining the sensitivity of tumor cells, stands out. The objective of the present study was to evaluate the cytoprotective/radioprotective effects of whole grape juices manufactured from the conventional or organic production systems, whether or not exposed to ultraviolet (UV-C) light irradiation. The results showed that I-131 presented a cytotoxic effect on human hepatocellular cells (HepG2/C3A) at concentrations above 1.85 MBq/mL, after 24 and 48 hours of treatment, though all concentrations (0.0037 to 7.40 MBq/mL) were cytotoxic to non-tumor human lung fibroblast (MCR-5) cells, after 48 hours. However, grape juices (10 and 20 µL/mL) did not interfere with the cytotoxic effect of the therapeutic dose of I-131 on tumor cells within 48 hours of treatment, while protecting the non-tumor cells, probably due to its high antioxidant activity. In accordance with their nutraceutical potential, antioxidant and radioprotective activity, these data stimulate in vivo studies on the use of natural products as radioprotectants, such as grape juice, in order to confirm the positive beneficial potential in living organisms.

A monocentric retrospective analysis about the effects of COVID-19 pandemic on emergency general surgery consultations.

OBJECTIVE: The pandemic effects due to the coronavirus SARS-CoV-2 caused a health emergency. We decided to carry out a study with the aim to investigate the changes in patients' tendencies for admission to the emergency department for surgical diseases, and the related hospitalizations and urgent surgery rates. PATIENTS AND METHODS: We carried out a retrospective, observational study on patients who received emergency general surgery consultation at our University Hospital during the two COVID-19 pandemic periods and on the same dates one year before. The patients' demographic characteristics, their hospitalization in surgical department and the data about those who underwent urgent surgery were retrospectively recorded. RESULTS: In the period March-April 2020 there were 95 surgical visits recorded; among these patients, 25% required hospitalization and 12.63% underwent urgent surgery. In the period November-December-January 2020-2021 there were 156 surgical consultations, of which 35.26% required hospitalization and 21.15% underwent urgent surgery. In both considered periods we found that the number of surgical consultations decreased compared to the same periods of the previous year. Moreover, we found a higher rate of hospitalization and need for urgent surgery. CONCLUSIONS: We documented a significant reduction in the overall number of surgical consultations and an increase of hospitalization and urgent surgery rates.

Preoperative sarcopenia predicts survival after hepatectomy for colorectal metastases: a prospective observational study.

OBJECTIVE: The surgical approach to colorectal liver metastases has highly improved the survival rates in metastatic colorectal cancer patients. Since sarcopenia estimates the physiologic reserve of an individual patient, it is considered a surrogate marker of patient frailty, and the selection of appropriate candidates for LR could be crucial to maximize the benefits derived from surgery. The present study investigated the impact of sarcopenia as a prognostic factor after LR from CRLM. PATIENTS AND METHODS: The study retrospectively analyzed 74 patients. Skeletal Muscle Mass at the third lumbar vertebra in the inferior direction was quantified using enhanced computed tomography scans. The patients were divided into two subgroups, with and without sarcopenia, based on median Skeletal Muscle Index. RESULTS: The study included 48 Sarcopenic patients and 26 Non Sarcopenic patients. The median follow-up considered for the patients was 32 months. Median SMI was 39.3 and 52.7 cm2/m2, respectively. The OS rate was significantly different between the two groups. Preoperative sarcopenia resulted in worse OS up to 48 months. CONCLUSIONS: Sarcopenia represents a negative prognostic factor as it is associated with poor postoperative OS. Future programs focused on remediating to the preoperative sarcopenic status of colorectal liver metastatic patients should be implemented.

The role of sarcopenia in the pancreatic adenocarcinoma.

OBJECTIVE: Pancreaticoduodenectomy is still associated with prolonged hospitalization and with a lot of complications. For these reasons, it is fundamental to improve strategies for preoperative risk stratification, and sarcopenia is one of the new identified markers of frailty. The purpose of our study was to retrospectively detect sarcopenia in patients undergoing pancreaticoduodenectomy and evaluate its importance as a preoperative marker. PATIENTS AND METHODS: We retrospectively identified a total amount of 76 consecutive patients who underwent pancreaticoduodenectomy for pancreatic head adenocarcinoma. Patients' and tumor's characteristics were recorded retrospectively. RESULTS: It appears that sarcopenia might be a useful preoperative prognostic factor for patients undergoing PD for PA. We found that Recurrence Free Survival may be influenced by presence or absence of preoperative sarcopenia, and we can confirm that in sarcopenic patients the average hospital stay is 20% longer than in non sarcopenic ones. CONCLUSIONS: Sarcopenia has a central role because it is a very common condition found in pancreatic cancer patients; there is growing evidence showing that it is associated with worse surgical outcomes. We can state that evaluating sarcopenia in cancer patients could improve the postoperative outcomes, overall survival rates and, nevertheless, the recurrence free survival ones.

Basics for surgeons about the immunohistochemistry role in pancreatic NETs diagnosis.

OBJECTIVE: Pancreatic neuroendocrine tumors (pNETs) are neuroendocrine tumors primarily found in the pancreas and upper small intestine. There are ten different pNETs: nine of these are associated with a specific functional syndrome, while one is not associated with a specific hormonal syndrome, and it is called non-functional. Up to 90% of pNETs are classified as non-functional. Immunohistochemistry is essential to define the diagnosis. However, to have a correct and reliable diagnosis, the pathologist must have adequately collected and treated tissue samples, thus the surgeon himself should be aware of some fundamental notions about tissue collection and fixation. Although several common biomarkers have been described to date, Chromogranin A and synaptophysin are currently considered the most specific immunohistochemical markers for NETs. Nearly 100% of pNETs are positive for both synaptophysin and Chromogranin A. Therefore, CgA and synaptophysin are effective for well-differentiated NETs but are less helpful in the diagnosis of poorly differentiated NECs, due to dedifferentiation, and then, degranulation of tumor cells. The Neuronal Specific Enolase (NSE) results to be an adequate marker in these cases. Considering the specific markers, many studies reported that endocrine pancreatic neoplasms are able to produce many different polypeptides and amines. Through immunohistochemical techniques, it is possible to define the diagnosis of pNET, which allows the clinicians to direct the patient to an effective therapeutic procedure. But to have a correct and reliable diagnosis, the tissue samples have to be adequately collected and treated.

A case report of three synchronous tumors in the same pancreatic specimen.

It is known that Duodenal adenocarcinoma (DA) is a rare malignant solid tumor that cause occlusion symptoms with orthodox dysphagia when locally advanced. Pancreatic neuroendocrine tumors (PanNETs) account for about 2% of all pancreatic neoplasms. The combination of these two lesions, with the synchronous presence of ectopic pancreatic tissue (EPT) of the duodenum, has never been described in literature, to our knowledge. Here we report a case of combined DA, EPT and PanNET affecting a 71-year-old woman.

Chemotherapeutical effects of the herbal medicine Uncaria tomentosa (Willd.) DC.

The use of medicinal plants dates back to the beginning of humanity, and today their application as complementary therapy has been widely disseminated as an alternative to conventional therapy. The medicinal plant named Uncaria tomentosa (Willd.) DC. (known as cat's claw) is a common woody vine of the Amazon forest that has traditionally been used in the treatment of arthritis because of its anti-inflammatory properties. This study aimed to evaluate the cytotoxic, mutagenic, and antimutagenic potentials of this medicinal plant. The biological activities of U. tomentosa were determined on bone marrow cells of Wistar rats that were treated in vivo. For the cytotoxic and mutagenic analyses, aqueous plant extract solutions were administered by gavage (1, 2, or 3 mg/mL) for 24 h (an acute treatment) or 7 days (a subchronic treatment). For the antimutagenic analyses, aqueous plant extract solutions (1 mg/mL) were administered by gavage before (pretreatment), simultaneous to (simultaneous treatment), or after (post-treatment), the administration of cyclophosphamide (1.5 mg/mL). U. tomentosa did not show any cytotoxic or mutagenic effects in any of the cytological or chromosomal analyses. Besides, the antimutagenic tests showed that the plant extracts displayed antimutagenic activities, which significantly reduced the percentages of the chromosomal aberrations that were induced by cyclophosphamide at 53.91, 58.60, and 57.03%, respectively, for the simultaneous treatment, pretreatment, and post-treatment. The results suggested a safe use of this herbal medicine that is available free of charge from the Brazilian Public Health System for the treatment of arthritis. This medicinal plant can also effectively contribute to improving the quality of life and the recovery of people undergoing chemotherapeutical treatments.

In vivo antimutagenic activity of the medicinal plants Pfaffia glomerata (Brazilian ginseng) and Ginkgo biloba.

Complementary and alternative therapies, including the use of medicinal plants, have become almost standard among the world's population. Pfaffia glomerata (PG), popularly known as Brazilian ginseng, is widely used as a restorer of vital functions, increasing mental balance, and is used for the treatment of diabetes and rheumatism. Ginkgo biloba (GB) is one of the oldest known gymnosperms, whose leaves are widely used for its potentiating action on the nervous system. The biological activities of these plants were determined on bone marrow cells of Wistar rats treated in vivo. For cytotoxic and mutagenic acute analysis, plant extracts were administered by gavage at concentrations of 0.15, 1.5, and 15 mg PG/mL water and 1, 2, and 3 mg GB/mL water. For antimutagenic analysis, plant extracts aqueous solution (PG, 1.5 mg/mL or GB, 2 mg/mL) were administered by gavage before (pretreatment), simultaneous to (simultaneous treatment), or after (post-treatment) the administration of cyclophosphamide (1.5 mg/mL, intraperitoneally). Both plant extracts have no cytotoxic or mutagenic potential, and they significantly reduce the percentage of chromosomal aberrations induced by the cyclophosphamide given simultaneously (PG, 87%; GB, 75%), pretreatment (PG, 98%, GB, 78%) and post-treatment (PG, 99%, GB, 75%). This beneficial antimutagenic property of the medicinal plants P. glomerata and G. biloba presented here, with no cytotoxic or mutagenic activity, can efficiently contribute to improvements in quality of life and recovery for people undergoing chemotherapeutic treatment, or those looking for health and preventive habits.

Influence of processing and storage of integral grape juice (Vitis labrusca L.) on its physical and chemical characteristics, cytotoxicity, and mutagenicity in vitro.

Integral grape juice is extracted from the grape through processes that allow the retention of their natural composition. However, due to the severity of some processes, fruit juices can undergo changes in their quality. The present study evaluated the cytotoxic and mutagenic effects of integral grape juice by a cytokinesis-blocked micronucleus assay in Rattus norvegicus hepatoma cells (HTC) in vitro. Vitis labrusca L. (variety Concord) were produced organically and by a conventional system, and their juice was extracted by a hot extraction process. The organic grapes were subjected to ultraviolet-type C radiation (UV-C). Experiments were performed after production and after 6 months in storage. Physicochemical analyses revealed that UV-C irradiation of organic grapes, the juice production process, and storage resulted in nutraceutical alterations. However, none of the juice concentrations were cytotoxic to HTC cells by the cytokinesis-blocked proliferation index results or were mutagenic, because the formation of micronucleated cells was not induced. In general, juice induced cell proliferation, possibly due to the presence of vitamins and sugar content (total soluble solid). The data increased the understanding of food technology and confirmed the quality and safety consumption of these juices.

In vivo antimutagenic effects of the Barbados cherry fruit (Malpighia glabra Linnaeus) in a chromosomal aberration assay.

Barbados cherry (BC) (Malpighia glabra Linnaeus) is a functional fruit that is consumed to prevent disease. It is used as an adjuvant in the treatment of several diseases, and acts as an antianemic, an appetite stimulant, a wound healer, an anti-inflammatory, a mineralizer, an antifungal, and an antioxidant agent. Several chemotherapeutic agents, such as cyclophosphamide, may result in undesirable side effects, and generate mutations in normal cells. Thus, the present study evaluated the antimutagenic potential of the fresh (BCN) and frozen (BCF) juices of BC pulp, with and without concomitant administration of cyclophosphamide, using a chromosomal aberration test system in the bone marrow cells of Wistar rats treated in vivo for 24 h. The results showed that neither the BC juice (0.4 mg/mL) alone, nor that with concomitant cyclophosphamide (1.5 mg/mL), were cytotoxic. BC has potential as an antimutagenic, and statistically reduced the percentages of chromosomal alterations induced by cyclophosphamide when administered simultaneously (BCN: 80.75%; BCF: 88.26%), pre-treatment (BCN: 86.85%; BCF: 87.32%), or post-treatment (BCN: 90.14%; BCF: 86.85%). This was due to the antioxidant activity of the fruit and the action of its bioactive compounds, which may have inhibited cyclophosphamide metabolism or scavenged the free radicals generated by this compound. Thus, attenuation of cyclophosphamide-induced mutagenicity suggests that the consumption of fresh or frozen BC should be encouraged for the prevention of disease, and for the maintenance and promotion of health.

Different responses of vanillic acid, a phenolic compound, in HTC cells: cytotoxicity, antiproliferative activity, and protection from DNA-induced damage.

The consumption of healthy and natural foods has increased over the last few years, primarily because these foods are rich in substances with biological properties of interest, such as exerting anticancer effects and decreasing oxidative stress in living tissues. These foods support adequate nutrition, maintain health, and improve quality of life. Vanillic acid (VA) is a phenolic compound used widely in the food industry as a flavoring, preservative, and food additive. VA can be found in various cereals, whole grains, fruits, herbs, green tea, juices, beers, and wines and possesses antioxidant, hepatoprotective, cardioprotective, and antiapoptotic activities. Studying the cytotoxicity as well as the mutagenic and antimutagenic effects of different concentrations of VA in Rattus norvegicus hepatoma cells (HTC) can identify new cellular activities of this substance. Concentrations up to 100 µM VA are not cytotoxic to HTC cells in a MTT [3-(4,5-dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide] assay after 96-h exposure; therefore, VA does not compromise mitochondrial activity. Similarly, concentrations up to 500 µM do not compromise plasma membrane integrity. VA at 10 and 50 µM showed no mutagenic/clastogenic effects, as no significant micronuclei induction was observed. VA 10 µM presented no antiproliferative activity and reduced the cytotoxicity induced by benzo[a]pyrene. The antimutagenic activity of 10 µM VA was observed by the simultaneous, pre-, and post-treatments, as the phenolic compound significantly reduced the frequency of micronuclei induced by the mutagen. These results indicate that VA exerts different responses in HTC cells. Low concentrations present no cytotoxic, mutagenic, or antiproliferative effects and protect cells from DNA damage.

Antimutagenic and radioprotective activities of beta-carotene against the biological effects of iodine-131 radiopharmaceutical in Wistar rats.

Radioactive iodine-131 (131I) is used in the treatment and diagnosis of thyroid gland injuries. However, because it emits ionizing radiation, it causes harmful effects to cells. Given that beta-carotene (BC) has antioxidant and antigenotoxic properties, this study aimed to investigate its radioprotective and antimutagenic activity in relation to 131I at the dose that is used to treat hyperthyroidism using a test system of bone marrow cells from Wistar rats (Rattus norvegicus). The doses were 0.2 mL of 8 mg BC/mL corn oil and 25 µCi 131I per 100 g body weight, and they were given via gavage in acute and subchronic treatments. Treatment groups included simultaneous, pre-treatment, post-treatment, and continuous treatment types. In all antimutagenic acute treatments, BC had a significant antimutagenic/radioprotective activity in relation to 131I. In subchronic antimutagenic treatments, BC reduced the damage that was caused by the radioisotope; however, this reduction was not statistically significant because of the relatively low percentage of chromosomal abnormalities that were observed with only 131I compared to the acute treatment. These results demonstrate the radioprotective and antimutagenic activity of BC, indicating its use by the population, which inevitably is exposed to mutagenic agents, as a means of health protection.

Cytotoxicity and mutagenicity of fluoxetine hydrochloride (Prozac), with or without vitamins A and C, in plant and animal model systems.

Fluoxetine, commonly known as Prozac, is the first representative of the so-called new generation of antidepressants that promise efficacy, with few side effects, against deep depression, nervous bulimia, and anxiety. As there is a growing number of people suffering from anxiety and depression; consequently, the use of fluoxetine is also increasing. Verifying absence of drug effects such as cytotoxicity or mutagenicity is of great importance. Certain vitamins, such as vitamin A (retinol, retinoids) and vitamin C (ascorbic acid) protect and are extremely active against mutagens. We evaluated the cytotoxic and mutagenic activity of fluoxetine, with and without concomitant administration of vitamin A or C, in Allium cepa meristem cells and Wistar rat bone marrow cells. The A. cepa meristem cells showed fluoxetine cytotoxicity; concomitant treatment with vitamin A or C proved non-protective. Treatment of Wistar rats with fluoxetine intraperitoneally or via gavage did not affect cell division or cause clastogenic effects. Vitamin A and C did not affect the cytotoxicity or mutagenicity of fluoxetine in the rat cells.

Cytotoxic and mutagenic effects of iodine-131 and radioprotection of acerola (Malpighia glabra L.) and beta-carotene in vitro.

The radioisotope iodine-131 [(131)I] can damage DNA. One way to prevent this is to increase the amount of antioxidants via dietary consumption. The goal of this study was to evaluate the radioprotective effect of fresh acerola pulp and synthetic beta-carotene in Rattus norvegicus hepatoma cells (HTC) in response to [(131)I] exposure in vitro. Cellular DNA damage was subsequently assessed using a cytokinesis block micronucleus assay. The mutagenic and cytotoxic activities of doses of [(131)I] (0.1, 0.5, 1, 5, and 10 µCi), acerola (0.025, 0.125, and 0.25 g acerola pulp/mL), and beta-carotene (0.2, 1, and 2 µM) were evaluated. Radioprotective tests were performed by simultaneous treatment with acerola (0.25 g/mL) plus [(131)I] (10 µCi) and beta-carotene (0.2 µM) plus [(131)I] (10 µCi). Acerola, beta-carotene, and low concentrations of [(131)I] did not induce micronucleus formation in HTC cells; in contrast, high concentrations of [(131)I] (10 µCi) were mutagenic and induced DNA damage. Moreover, neither acerola nor beta-carotene treatment was cytotoxic. However, acerola reduced the percentage of [(131)I]-induced damage, although beta-carotene did not show a similar effect. Thus, our results suggest that acerola diet supplementation may benefit patients who are exposed to [(131)I] during thyroid diagnostics and therapy.

Possible modulating actions of plant extracts on the chromosome breaking activity of MMC and Ara-C in human lymphocytes in vitro.

Plants popularly used as medicine have been seen as promising natural agents by the pharmaceutical industry. In the present study the action of Psidium guajava L. (Pg) and Achillea millefolium L. (Am) infusions on chromosomal aberration formation in human lymphocyte system in vitro was assessed, associating them with the alkylating agent mitomycin C (MMC) and the DNA repair inhibitor cytosine-beta-arabin-furanoside (Ara-C). The cells were cultivated for 72 h and treated continuously with Pg and the Am infusions at dosages of 2.62 x 10(-4) g and 3.5 x 10(-4) g/ml culture medium, respectively. Treatments with MMC (0.30 microg/ml) or Ara-C (5 x 10(-7) microg/ml) were administered after 48 h of cell culture. Each samples (five individual) were exposed to nine treatments (control with PBS; Pg; Am; MMC; MMC+Pg; MMC+Am; Ara-C; Ara-C+Pg; and Ara-C+Am) and 100 cells were analyzed per cell culture. The used doses of each infusion did not cause clastogenic effects significantly different to the negative control (control=1%; Pg=2.2%; Am=1.8%). Nevertheless, the aberrant cell frequency after MMC treatment was significantly increased by the Am infusion (MMC=32.4%; MMC+Pg=36.2%; MMC+Am=44%), especially when the chromatid break types number was scored (MMC=151; MMC+Pg=173; MMC+Am=249). Regarding DNA repair inhibition by Ara-C, the Pg infusion caused a significant reduction in aberrant cell frequency (Ara-C=15.8%; Ara-C+Pg=11%; Ara-C+Am=14.4%), only when the chromatid break types number was scored (Ara-C=63; Ara-C+Pg=40; Ara-C+Am=58). These results indicate that the plant infusions per se do not have clastogenic activity, but can influence the clastogenic action of MMC and Ara-C on DNA break induction, in vitro.

Anticlastogenicity of chlorophyllin in the different cell cycle phases in cultured mammalian cells.

Chlorophyllin (Chln), a sodium-copper salt derivative of chlorophyll, like chlorophyll-a and -b found in green plants, has been studied for its protective action against the carcinogenic effects of various physical and chemical agents and in relation to the mutagenic and clastogenic activities of genotoxic agents. The aim of the present study was to evaluate chlorophyllin in different phases of the cell cycle for clastogenicity and anticlastogenicity, the latter in reversing DNA damage induced by ethyl methane sulfonate (EMS). The test for chromosomal aberrations was performed in cultured mammalian cells (CHO-K1). The three Chln concentrations tested (6.25, 12.5 and 25 microg/ml) were not clastogenic and damage induced by EMS (1240 microg/ml) was reduced in cells treated with Chln as well during S (25-48%) and G2/S (70-80%). The results demonstrate a greater protective effectiveness of Chln against EMS during G2/S.

Investigation of genotoxic and antigenotoxic activities of chlorophylls and chlorophyllin in cultured V79 cells.

Chlorophyll and its derivatives are examples of plant compounds (purified and/or extracted) which appear to protect DNA from damage caused by chemical or physical agents, although some studies have identified clastogenic activity of these compounds. This study was carried out to assess the genotoxic activity of chlorophyll-a (Chl-a), -b (Chl-b) and chlorophyllin (Chl) and their antigenotoxic activity against the DNA damage induced by methyl methanesulphonate (MMS) under conditions of simultaneous, pre-, post-treatment, and simultaneous treatment after pre-incubation of the chemical with MMS. The micronucleus (MN) test was used in binucleated cells (induced by cytochalasin-B) of a mammalian cell line (V79). The three concentrations of Chl-a, Chl-b or Chl (0.1375, 0.275, 0.55microM) were not genotoxic and the genotoxic action of MMS (400microM) decreased (74-117%) under all treatment conditions. The results showed that there was no significant difference among the treatment types, the concentration or the nature of chlorophyll used. The data obtained suggest that Chl-a, Chl-b and Chl when associated with the DNA damaging agent, MMS, may protect the DNA by desgenotoxic action and/or by bio-antigenotoxic mechanisms, with the similar efficiency.