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Biomedical subjects

H F Stich

Publications and source records attributed to H F Stich.

At least 37 records · Page 2Linked to original sources
PubMed1988

Effect of retinoic acid on bovine papillomavirus (BPV) DNA-induced transformation and number of BPV DNA copies.

The effect of all-trans-retinoic acid (RA) was examined on (1) transformation induced in C127 cells by transfection with plasmid pdBPV-1 (142-6), which contains DNA of bovine papillomavirus (BPV), (2) the capacity of transformed BPV DNA-containing clones to form colonies with transformed properties (e.g., piling up into multilayered colonies), and (3) the number of BPV DNA copies in transformed cells. At nontoxic doses ranging from 10(-7) to 10(-5) M, RA reduced the frequency of transformed foci in a dose-dependent manner. The extent of inhibition depended on the length of RA treatment and on the time that elapsed between DNA transfection and RA treatment. RA exerted only a slight inhibitory effect during the first days after transfection. Complete inhibition was observed when the cells were continuously exposed after transfection to RA at doses ranging from 0.5 to 1 X 10(-5) M. The inhibitory effect of RA on transformation was reversible. Transformed foci started to form after withdrawal of RA treatment. In the presence of RA (5 X 10(-6) M), cells from transformed colonies were no longer able to form foci displaying transformed properties. The number of BPV DNA copies gradually decreased when the cells were grown over several generations in the presence of RA (5 X 10(-6) M). After approximately 30 cell generations, the cell cultures appeared to have less than one copy of BPV DNA.

Animals↗
PubMed1988

Response of oral leukoplakias to the administration of vitamin A.

Tobacco/betel nut chewers (Kerala, India) with well-developed oral leukoplakias were chosen for a short-term intervention trial of vitamin A therapy. Participants were randomly distributed into two groups, one receiving 200,000 IU vitamin A per week (0.14 mg/kg body wt/per day) for 6 months, and the other receiving placebo capsules. Their cancer-causing habit, which can be quantitated (an average of 13.1 betel quids/day, 26.1 min/quid), did not change during the trial period. The 6-month oral administration of vitamin A caused complete remission in 57.1% of participants, and a total suppression of the development of new leukoplakias in all chewers receiving vitamin A (n = 21), as compared to 3% and 21%, respectively, in the placebo group (n = 33). The results were substantiated by examining the histological and cytological changes on small biopsies which were taken at the onset and at the completion of the trial period. Over the 6-month period of vitamin A administration, the number of layers of spinous cells decreased in 85% of the participants, the loss of polarity of basal cells was reduced from 72.2% to 22.2% of chewers, subepidermal lymphocytic infiltration was greatly diminished from 66.7% to 5.5% of chewers, and nuclei with condensed chromatin disappeared from the epidermal layer (72.2% before to 0% at the end of the trial).

Adult↗
PubMed1988

Chromosome aberrations in cultured central mudminnow heart cells and Chinese hamster ovary cells exposed to polycyclic aromatic hydrocarbons and sediment extracts.

1. Genotoxicity experiments were conducted with cultured fish cells to determine if the high frequency of epidermal papillomas observed in lemon sole from Sturgeon Bank, where a sewage treatment plant discharges, could be correlated with contamination of the sediments with chemicals such as 3,4-benzopyrene. 2. The frequency of chromosome aberrations was measured in cultured Umbra limi heart (U1-H) and Chinese hamster ovary (CHO) cells following exposure to the polycyclic aromatic hydrocarbons (PAH) 3,4-benzopyrene (BP), 1,2,5,6-dibenzanthracene (DBA), 1,2-benzanthracene (BA), and pyrene (PY), activated using S9 prepared from rainbow trout liver. 3. An increase in the chromosome aberration frequency was only observed following exposure to fish S9-activated BP in both cell lines. 4. Following exposure of the cells to both Sturgeon Bank and Spanish Bank sediment extracts, it was determined that a higher level of toxic and genotoxic activity was associated with the Sturgeon Bank sediments. 5. Since the detection of PAH genotoxicity requires the presence of S9, and since a higher level of genotoxic activity was noted following sediment extract exposures with no S9 present, this suggests that the extracts contain a complex mix of chemicals, some of which express genotoxic activity. 6. An assessment using the micronucleus test failed to indicate in vivo genotoxicity in fish collected from Sturgeon and Spanish Banks. 7. It was, therefore, difficult to associate the observed sediment genotoxicity with the previously noted high incidence of epidermal papillomas in lemon sole from this area.

Animals↗
PubMed1988

DNA adducts, micronuclei and leukoplakias as intermediate endpoints in intervention trials.

Internal dosimeters that can provide information about responses to chemopreventive agents in a short time would be invaluable for planning treatment protocols for large-scale intervention trials. Micronuclei meet many of the prerequisites of a good intermediate endpoint. They can be quantified in cultured cells, animal tissues and human exfoliated cells and biopsies. With image scanning, up to 10(5) cells can be screened for micronuclei within a few minutes. The predictive value of micronuclei has been demonstrated using cultured cells exposed to carcinogens and chemopreventive agents and using oral mucosa of betel-quid chewers. DNA adducts, as detected by 32P-postlabelling techniques, could conceivably be another potentially useful marker. However, prior to their use in intervention trials, interindividual variations in their levels in primary, secondary and nontarget tissues and the relationship with doses of carcinogens must be established. The wide scatter of DNA adduct levels in the bronchial mucosa of smokers and of nonsmokers reveals one difficulty that can be encountered using this marker in intervention trials.

Animals↗
PubMed1987

Tobacco-specific nitrosamines in the saliva of Inuit snuff dippers in the Northwest Territories of Canada.

Levels of tobacco-specific nitrosamines (TSNA), nicotine and cotinine were estimated in the saliva of 20 snuff dippers (Inuit, Northwest Territories, Canada). Levels of N'-nitrosonornicotine (NNN), 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosoanatabine (NAT) plus N-nitrosoanabiasine (NAB) found in the saliva following a 15-min period of keeping 0.5-1.5 g of moist snuff in the gingival groove are considerable: 115-2610 ppb NNN, 123-4560 ppb NAT + NAB, and up to 201 ppb NNK. The amount of TSNA in the saliva increases with the length of time that the snuff is kept in the mouth. The estimated total amount of 444 micrograms TSNA, the largest part of which will be swallowed, exceeds by far the amounts of nitrosamines ingested through drinking beer (0.34 micrograms/day), eating cured meat products (0.17 micrograms/day), or using cosmetics (0.41 micrograms/day). The relatively high levels of potentially carcinogenic TSNA in the saliva, together with the current popularity of snuff usage by teenagers, is of particular concern.

Canada↗
PubMed1987

DNA repair synthesis in cultured fish and human cells exposed to fish S9-activated aromatic hydrocarbons.

Unscheduled DNA repair synthesis was measured autoradiographically in cultured rainbow trout gonad (RTG) and human fibroblast (HF) cells following exposure to aflatoxin B1 (AFB1), 3,4-benzopyrene (BP), 1,2,5,6-dibenzanthracene (DBA), 1,2-benzanthracene (BA) and pyrene (PY) activated with S9 prepared from rainbow trout liver. S9 from rainbow trout injected with Arochlor 1254 or an oil extract was compared with S9 from Fischer rats injected with Arochlor 1254 for the ability to activate AFB1 and cause DNA repair in RTG and HF cells. All three types of S9 activated AFB1, but the measured DNA repair response was greater in the HF cells. A significant grain count response was found following exposure of HF cells to fish S9-activated BP. Using assay conditions which enhance fish cell grain counts, a significant level of DNA repair was also found in RTG cells exposed to fish S9-activated BP. Marginal but statistically significant amounts of DNA repair were elicited in HF and RTG cells exposed to rainbow trout S9-activated BA and DBA, but no response was detected following PY exposure. Fish S9 was found to be able to activate a series of polycyclic aromatic hydrocarbons (PAH) and cause DNA repair synthesis in both fish and mammalian cells. The magnitude of the repair response roughly parallels the carcinogenic potential of the PAHs. These results elicit trans species and phyla comparisons which help to validate fish as models for aquatic carcinogenesis research, and also demonstrate PAH DNA-damaging effects on fish DNA, adding further credence for studying the effects of these chemicals on aquatic organisms.

Aflatoxin B1↗
PubMed1987

Use of intermediate endpoints in quantitating the response of precancerous lesions to chemopreventive agents.

A current area of emphasis in cancer research is the determination of whether cancer can be prevented through the use of naturally occurring chemopreventive agents such as beta-carotene. A major area of concern in the design of long-term, large-scale population studies to ascertain the efficacy of such chemopreventive agents lies in the paucity of biological data on the activity of these agents in man. The studies described in this paper were performed to determine whether a series of short-term markers could be used in chemopreventive trials as indicators of the possible success of a chemopreventive regime. Three such markers are described. The first involves the measurement of genotoxic damage in the target tissues of carcinogen-exposed individuals by using the micronucleus test on exfoliated cells. This end point has been successfully used to demonstrate a reduction in carcinogen damage (micronuclei production) in the oral cavity of individuals in population groups at elevated risk for oral cancer (tobacco and betel quid users in the Philippines, snuff users in the Northwest Territories). The second marker involves the determination of DNA adducts in exfoliated cells of carcinogen-exposed individuals by the use of DNA postlabelling procedure. The final marker discussed involves a chemical determination of the levels of a chemopreventive agent in target tissues of individuals receiving a supplement in the diet. In this case, the example described is beta-carotene in exfoliated cells of carcinogen-exposed individuals. These three markers may be combined to determine whether a chemopreventive agent reaches a target tissue, affects DNA adduct formation, and prevents genotoxic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Relationship between cellular levels of beta-carotene and sensitivity to genotoxic agents.

The usefulness of an in vitro test system to predict the inhibitory effect of beta-carotene on the genotoxic activity of carcinogens/mutagens was explored. To facilitate the comparison of data obtained from cultured cells (CHO) and from exfoliated human cells, endpoints were used which can be quantitated in both cell systems: the frequency of micronuclei for estimating the effect of genotoxic agents, and cellular levels of beta-carotene as a protective agent. In CHO cells, beta-carotene inhibited the clastogenic and micronucleus-forming effect of methyl methanesulfonate (MMS) and 4-nitroquinoline-1-oxide (4NQO), but had no protective action against gallic acid, tannic acid, and aqueous extract of areca nut or H2O2. The extent of inhibition depended on the ratio of beta-carotene to MMS. Doses of beta-carotene which exerted a protective effect in vitro ranged from approximately 2 to 5 ng per 10(6) CHO cells. Comparable levels of beta-carotene were previously found to reduce the frequency of micronucleated exfoliated cells from the buccal mucosa of tobacco and areca-nut chewers (Stich et al., 1984b).

4-Nitroquinoline-1-oxide↗
PubMed1986

Beta-carotene levels in exfoliated mucosa cells of population groups at low and elevated risk for oral cancer.

Beta-carotene was estimated in exfoliated oral mucosa cells in groups of individuals at various risks for oral cancer. Approximately 4 X 10(6) exfoliated cells were collected from each subject by brushing the oral mucosa. Cell pellets were hydrolyzed with pronase and then with KOH/methanol. Beta-carotene was extracted with hexane, separated by reverse-phase HPLC, and detected at 450 nm. Mean beta-carotene levels in exfoliated cells were 0.08 ng/10(6) cells for 56 heavy consumers of alcoholic beverages (150 g or more per week), 1.36 ng/10(6) cells for 28 Seventh Day Adventists (all abstainers from alcohol, tobacco and meat consumption), 1.39 ng/10(6) cells for 55 lacto-vegetarians of the International Society for Krishna Consciousness (ISKC) (abstainers from alcohol and tobacco), and 1.08 ng/10(6) cells for 61 representatives of a "Western" life-style pattern (64% consumed the equivalent of at least one bottle of wine or 7 bottles of beer per week, and all were non-smokers). If the heavy alcohol consumers (males) are matched to non-drinking males of comparable age, the mean beta-carotene values are 0.08 ng versus 1.24 ng/10(6) cells. The possible involvement of the low levels of beta-carotene in the mucosa of heavy alcohol drinkers in increased sensitivity towards the carcinogenic and genotoxic activity of cigarette smoking plus alcohol ingestion is discussed.

Alcohol Drinking↗
PubMed1986

Beta-carotene levels in exfoliated human mucosa cells following its oral administration.

Beta-carotene levels of exfoliated oral mucosa cells can be increased severalfold by the oral administration of this provitamin. Beta-carotene was estimated by HPLC analysis in pronase-treated exfoliated cells obtained by brushing the entire oral mucosa with a toothbrush. A small percentage of individuals did not respond with an increase of beta-carotene in their mucosa cell in spite of a relatively large intake of the provitamin (360 mg in 4 days, or 2880 mg in 16 weeks, respectively). Levels of beta-carotene in the mucosa cells are affected by the concurrent administration of vitamin A: 0.27 ng beta-carotene per 10(6) cells in the placebo group, 1.79 ng following the intake of beta-carotene (180 mg/week for 16 weeks), and 4.29 ng after beta-carotene (180 mg/week for 16 weeks) plus vitamin A (100,000 IU/week for 16 weeks) consumption. The considerable variations in tissue levels of beta-carotene following its oral administration must be taken into account when cancer intervention trials using this agent are designed and evaluated.

Adult↗
PubMed1986

Oral lesions, genotoxicity and nitrosamines in betel quid chewers with no obvious increase in oral cancer risk.

A link between the generation of areca nut-related N-nitrosamines in the saliva, the induction of genotoxic damage in the oral mucosa, as judged by an increase in micronucleated exfoliated cells (MEC), and a low incidence of oral cancer was studied in 2 population groups characterized by their habit of chewing quids without tobacco: Guamanians, who chew areca nuts (Areca catechu) with or without the addition of betel leaf (Piper betle); Taiwanese, who use areca nut, betel leaf or inference and slaked lime. The levels of N-nitrosoguvacoline (NG) in the saliva of chewers of fresh green areca nuts were very high (70.8 ng/ml) as compared to those reported for individuals using the more complex Indian betel quids (0.91 ng/ml or 5.6 ng/ml). None of the other areca nut-related nitrosamines (N-nitrosoguvacine (NGC), 3-(methylnitrosamino)propionitrile (MNPN) and 3-(methylnitrosamino)propionaldehyde (MNPA)) were detected in the saliva of Taiwanese betel quid chewers. The addition of slaked lime to the areca nut enhances the formation of NG during a chewing session. The frequency of MEC did not increase in the oral mucosa of areca nut chewers who do not use slaked lime, but showed a small but significant elevation in individuals using lime-containing quids. The elevation of MEC in Taiwanese, who are at low risk for oral cancer, is relatively small as compared to that found in chewers of Indian betel quids (pan), who show a highly elevated oral cancer risk. The results seem to suggest that NG may play only a minor role, if any, in the etiology of oral cancer among betel quid chewers.

Areca↗
PubMed1986

Mechanism of inhibition of N-methyl-N'-nitro-N-nitrosoguanidine-induced mutagenesis by phenolic compounds.

At non-toxic concentrations, 2 naturally occurring phenolic compounds, caffeic acid and chlorogenic acid, suppressed the mutagenic activity of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium strain TA1535. The inhibitory effect was observed only when the phenolic compound and the mutagen were administered concurrently. The interaction between phenolic compounds and MNNG was also studied in a cell-free system using a colorimetric method. The results are consistent with the assumption that phenolic compounds scavenge reactive electrophilic MNNG degradation products, thereby preventing their action on critical cellular targets.

Caffeic Acids↗
PubMed1986

32P-postlabelling analysis of aromatic DNA adducts in human oral mucosal cells.

Exfoliated mucosal cells were collected from the oral cavity of three groups at high risk for oral cancer: Indian betel nut chewers, Filipino inverted smokers (burning end of cigar in mouth) and Indian Khaini tobacco chewers. DNA was extracted from these samples, as well as from samples of exfoliated cells of Canadian non-smoking controls. DNA was analyzed for the presence of aromatic DNA adducts using 32P-postlabelling analysis. Five chromatographically distinct adducts were found in samples from both the high risk groups and the nonsmoking controls. Individual adducts were detectable in approximately 30-95% of samples, depending on the adduct and population group. Estimated levels of specific adducts ranged from non-detectable (prevalence relative to normal nucleotides less than 1 X 10(-9)) to occasionally greater than 1 X 10(-7). No adducts were found in high risk groups which did not also appear in control subjects.

Adenosine Triphosphate↗
PubMed1986

The effect of nass use and smoking on the risk of oral leukoplakia.

The results of a survey of a population with a high incidence of oral cancer are presented in this paper. A remarkably high proportion (41%) of the men surveyed used nass, which is a mixture of tobacco, lime, ash, and cotton oil. The prevalence of oral leukoplakia, lesions thought to be a precursor of oral cancer, was high in persons who used nass (12%) and who smoked cigarettes (15%), and highest among those men who both used nass and smoked (21%). It has been shown that nass use increases the frequency of micronucleated cells in the exfoliated sublingual cells. The clastogenic and genotoxic effect of nass revealed in the study could be attributed to the presence of tobacco-specific N-nitroso compounds. However, the results of chemical analysis, which has shown that nass contains relatively low levels of these compounds, suggest that the relatively strong genotoxic activity of nass could primarily be associated with other chemicals, possibly oxidized phenolics. Despite the uncertainty as to which of the chemicals contained in nass are involved in the etiology of oral cancer and what exactly are the mechanisms of nass-induced carcinogenesis, the results of this study suggest that in populations where nass is widely used, oral leukoplakia and, most probably, oral cancer are conditions that could be prevented by the elimination of nass use and cigarette smoking.

Aged↗
PubMed1985

A pilot beta-carotene intervention trial with Inuits using smokeless tobacco.

The frequency of exfoliated cells with micronuclei (MNC) was used to estimate the genotoxic effect of smokeless tobacco (snuff) on the oral mucosa and to follow the response to the administration of beta-carotene (180 mg/week, given twice weekly in 6 capsules of 30 mg each). The pilot trial was carried out with Inuits in Gjoa Haven, Northwest Territories, Canada. Their traditional diet, which is rich in caribou and seal meat and liver but low in vegetables and fruits, leads to "normal" serum levels of retinol (447 ng/ml in non-users of tobacco and 463 ng/ml in tobacco users) but low levels of beta-carotene (57 ng/ml for non-users of tobacco and 47 ng/ml for users). Prior to the twice-weekly administration of beta-carotene, the frequency of MNC was 1.87% +/- 0.92 (n = 23) in the mucosa of the lower gingival groove where the tobacco was usually kept. It decreased significantly (P less than 0.001) to 0.74% +/- 0.42 following the 10-week oral administration of beta-carotene capsules. The frequency of MNC did not change significantly in the group receiving a placebo and in snuff users who received no treatment over the 10-week trial period. The size and morphological appearance of the typical snuff-related, whitish, wrinkled patches of the mucosa where the tobacco was kept was not affected by the 10-week treatment with beta-carotene. Similarly, no reduction was observed in the frequency of anucleated, exfoliated mucosa cells. Beta-carotene appears to be an efficient inhibitor of MNC in the oral mucosa of snuff users who do not suffer from any vitamin A deficiency and who have "normal" levels of retinol.

Adolescent↗