Hepatic subcellular storage of beta-carotene in rats following diet supplementation.

Beta-carotene (BC) storage was measured in liver and its subcellular fractions (plasma membranes, mitochondria, microsomes and nuclei) of rats fed BC added to diet. The BC supplementation dose was about 350 mg/week/rat. After 15 weeks of this supplementation, rats were killed and their livers were immediately excised and processed to obtain total liver tissue and its subcellular fractions. Their BC contents were measured by HPLC as pmols/mg. protein Intact BC was found to be stored in all the above subcellular fractions, thus showing that BC is probably taken up by liver cell lipid moiety. Interestingly, the mean BC concentrations in plasma membranes and mitochondria were significantly higher than that in total liver tissue. Our data confirmed that rodents are a good animal model for the study of BC metabolism and its effects on several pathologies, and cancer prevention and treatment in humans in spite of the fact that rodents are classified as white-fat animals because of their poor BC absorption and storage in fat and blood plasma, whereas humans are classified as yellow-fat organisms because of their opposite behavior in BC uptake and organ distribution.

Human lymphocyte micronucleus genotoxicity test with mixtures of phytochemicals in environmental concentrations.

This study was carried out to assess the genotoxicity of mixtures of pesticides using the micronucleus test with human lymphocytes in culture. Benomyl, azinphos-methyl, diazinon, dimethoate, pirimiphos-methyl pesticides were tested at doses estimated from their daily intake (EDI). Benomyl is a carbamate fungicide, the other compounds are organophosphorous insecticides. The compounds were tested both separately and in combination. The results showed a weak genotoxicity for three of the four organophosphorous insecticides and for benomyl. The various mixtures did not give additive effects.

Carotenoids in cancer, mastalgia, and AIDS: prevention and treatment--an overview.

In 1980, two carotenoids, beta-carotene (BC) and canthaxanthine (CX) with and without pro-vitamin A activity, respectively, were orally administered to female Swiss albino mice and were found to substantially prevent skin carcinogenesis induced by benzo(a)pyrene (BP). This preventive effect was observed in darkness by means of photocarcinogenic enhancement (PCE) following UV (300 to 400 nm) irradiation. In 1984, the same experiment produced antitumorigenic activity when applied to breast carcinogenesis induced in mice by 8-methoxypsoralen (8-MOP) plus UV-A light and, in 1985, when directed toward gastric carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). These data suggested a rationale for human intervention to prevent, by carotenoid supplementation, a second primary malignancy after the primary malignancy has been radically excised. In the 1980s, a pilot clinical study (15 cases) showed a longer than expected disease-free interval in all surviving patients. It was also subsequently found that, if treated daily with 20 mg of BC and intermittently with retinol 150 to 300,000 IU daily for seven days just prior to menses, women suffering from cyclical mastalgia were relieved from pain, without any toxic side effects. When BC was given in high daily doses (60 mg) to 60 drug addicts suffering from AIDS-related complex (ARC), they recovered from their objective and subjective symptoms (but not from lymphadenopathy) with improvement in their general health and increased performance status. At higher doses, BC (with or without hyperthermia) was effective even in patients in advanced stages of AIDS. A debate has arisen concerning a recent statement by the U.S. Government that "beta-carotene supplements do not protect Americans against cancer or heart disease, and may actually increase the risk of deadly lung tumors in smokers".

Whole body hyperthermia associated with beta-carotene supplementation in patients with AIDS.

The objective of this work was to check possible additive beneficial effects of whole body hyperthermia (WBH) associated with beta-carotene (BC) supplementation in patients with AIDS. In a pilot study, 10 HIV positive patients, (8 with AIDS and 2 with AIDS related complex, ARC), after AZT or DDI discontinuation, were first treated with one single session of WBH applied with a non-invasive procedure at 42 degrees C core temperature for one hour, and subsequently supplemented with BC 120 mg daily continuously. All patients well tolerated the non-invasive WBH as well as the high dose BC supplementation. Apart from one patient who died after 4 months, all the others underwent an HIV burden diminution, clinical improvement and amelioration of laboratory data, along with an subjective improvement of their life quality. With reference to control groups, namely (a) only WBH applied with extracorporeal procedure to 31 AIDS patients, and (b) only BC supplementation at high dosage applied to 64 ARC patients, the combined physical and BC supplemental treatments clearly showed a better and longer lasting response.

Giant cell formation in Hodgkin's disease.

The identity of Reed-Sternberg cells in Hodgkin's disease has remained an unresolved issue, though many studies have addressed this question. Giant cells are usually formed either by endomitosis without cytoplasmic division or by cell fusion through cytokines or viruses. Growing evidence associates Epstein-Barr virus (EBV) with Hodgkin's disease, a major issue being whether EBV is a passenger virus or has an aetiological role. This communication describes experimental conditions enabling observation of giant cell cytogenesis from peripheral blood mononuclear cells in culture. Mononuclear cells were isolated from autologous peripheral blood and cocultured with a single-cell suspension obtained from Hodgkin's lymph nodes in a culture chamber where the two cell populations are isolated by a microporous membrane that allows only cytokines and viruses to pass through. Under these experimental conditions, giant cells are formed in the peripheral blood mononuclear cell fraction; some of them appear morphologically indistinguishable from Reed-Sternberg cells and their mononuclear variant, while others much resemble Langhans giant cells. Some of these giant cells are positive for EBV DNA by in situ hybridization. These results suggest that an EBV-dependent biological activity is responsible for giant cell cytogenesis originating from lymphocytes and monocytes, induced either by EBV and/or cytokines.

beta-Carotene storage in rat organs following carrier mediated supplementation.

One rat group was supplemented with beta-carotene (BC) both in beadlets and the crystalline form in arachidic oil as a carrier added to standard diet; another rat group was given 1 ml crystalline BC-arachidic oil by gavage twice a week. In both rat groups, each rat ingested 350 mg BC/week for 12 weeks. The animals were then sacrificed and BC levels together with retinyl palmitate presence were assessed by HPLC analysis in liver, lung, kidney, small intestine, mesenteric fat, brain, spleen, stomach and blood plasma. In the first group, high BC storage, ranging from 4.2 to 45.2 nmols/g wet tissue, was found in liver, small intestine, spleen; lesser BC levels were found in lung, kidney, stomach, blood serum; retinyl palmitate was found in liver and lung. In the second group BC levels ranging from 0.5 up to 5,763 nmols/g wet tissue were detected in all organs, except for brain and stomach; the highest levels were in the lung; retinyl palmitate was detected in liver. The lung appeared to be a target organ for BC, as confirmed by its presence in the lungs of control rats fed standard diet and given 1 ml of arachidic oil alone by gavage twice a week.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotenoids in cancer chemoprevention and therapeutic interventions.

Carotenoid (CARs: beta-carotene BC and/or canthaxanthin CX) supplementation have been shown to be chemopreventive in animals, since 1980, against direct or indirect chemical carcinogenesis/photo-carcinogenesis of the skin, breast, stomach, salivary glands, colon-rectum, urinary bladder, and against transplanted tumors. This action could be either independent of or dependent on pro-vitamin A activity of BC. In vitro, both BC and CX proved to be antimutagenic and to have anti-malignant transformation properties in cell cultures. Preliminary interventions in humans with BC +/- CX prevented the onset of second primary tumors in lung, colon, urinary bladder, and head and neck. The powerful antioxidant properties of CARs, possibly associated with their retinoid potential, played a role in all the above observations, producing free-radical quenching and immunostimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Short communication: possible activity of beta-carotene in patients with the AIDS related complex. A pilot study.

In a pilot single blind study, beta-carotene (BC) supplementation produced, in ARC patients under current treatment, apparent recovery from asthenia, fever, nocturnal sweating, diarrhoea, loss in weight, and led as a result to an improvement in general health and working efficiency, but not to an improvement in multiple district lympho-adenopathies. Nevertheless, BC appeared to prevent progress to AIDS and, in addition, to lower the effective dosage of AZT used in one case of ARC developed into AIDS, producing a recovery from opportunistic infections and an inhibition of Kaposi sarcoma diffusion, in line with a two-fold rise in CD4 counts.

Free radicals as carcinogens and their quenchers as anticarcinogens.

An oxygen dependent signal was detected, late in the 1950s by electron spin resonance (ESR) in a saline solution of hematoporphyrin (Hp) excited by light. This signal expressed a free radical consisting of 'some kind of an association between Hp and oxygen', that Smaller et al. called 'oxyradical' (HpOO.). It soon opened a new level of understanding in carcinogenesis triggered by photodynamic substances, including Hp itself, polycyclic hydrocarbons (PCHs), as well as any carcinogen involving molecular species activated by radiation and/or metabolic reaction. Early in the 1960s, this prompted the discovery of benzo(a)pyrene (BP) photocarcinogenic enhancement (BP-PCE) in mice, probably due to an increase in free oxygen radical generation following correct light exposure. This assumption was confirmed in 1980 by the fact that mice orally loaded with antioxidants and radical quenchers, such as beta-carotene (BC) and cantaxanthin (CX), were protected against BP-PCE at 100% and against total BP carcinogenicity at more than 60%. These achievements were presented as the bases of the current explosion of interest in biology and medicine in building up the new field of chemoprevention against cancer and other chronic diseases by supplementation with antioxidant vitamins, retinoids and especially carotenoids and their synergistic association. The relevant findings of this research obtained in the last decade in in vitro and in vivo experiments as well as human interventions are reported and discussed with personal contributions.

Beta-carotene supplementation associated with intermittent retinol administration in the treatment of premenopausal mastodynia.

Twenty-five women, 23-41 year old, suffering from premestrual cyclical mastodynia linked or otherwise to benign breast disease (BBD), with moderate or severe pain at least seven days before each menstrual period, were treated with daily beta-carotene (BC) supplementation associated with intermittent administration of retinol (all-trans-retinol 300,000 IU per day). In this therapy retinol was given for 7 days immediately before each menstrual period. After 6 months' treatment, the results revealed marked reduction in breast pain, and sometime recovery, in 23-41 year old women with no toxic side effects. But no such advantages in 5 women with non-cyclical mastodynia treated as above were found. Above this age range, the advantages appear to be absent. All the women developed a healthy look because of a slight tanning of the skin due to beta-carotene supplementation. These data demonstrated a therapeutic synergism between BC and retinol.