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Biomedical subjects

C Maltoni

Publications and source records attributed to C Maltoni.

At least 55 records · Page 3Linked to original sources

Quantitative histochemistry of benzaldehyde dehydrogenase in hepatocellular carcinomas of vinyl chloride-treated rats.

Hepatocarcinogenesis in rats treated with several chemicals is associated with changes in aldehyde dehydrogenase (AlDH) activity, particularly heterogeneous expression of a "tumor specific" phenotype that is very active with aromatic aldehydes, e.g., benzaldehyde (Bz). Objectives of this study were first, to determine if liver cancers in vinyl chloride-treated rats also expressed this AlDH phenotype, and second, to quantitate the NAD- and NADP-dependent AlDH activity for the substrates Bz and acetaldehyde (Ac) in the cancers and surrounding tissue. Small cubes of tissue containing well-differentiated hepatocellular carcinoma were obtained from five Sprague-Dawley rats exposed to 2500 ppm vinyl chloride for 55 weeks. An optimized procedure was developed for AlDH histochemistry. Frozen sections were preincubated in nitroblue tetrazolium/acetone and then incubated at 20 degrees C in viscous polyvinyl alcohol media containing buffer, phenazine methosulfate, sodium azide, substrate, coenzyme, and nitroblue tetrazolium. Background activity was evaluated by omission of substrate. Activity was quantitated by computer-assisted microscopic photometry. All five carcinomas had heterogeneous staining of NADP- and NAD-dependent BzDH and AcDH activity, with clusters of very high-activity cells. The magnitude of staining in the high-activity neoplastic cells was at least tenfold greater for BzDH-NADP and about twofold greater for BzDH-NAD, AcDH-NADP, and AcDH-NAD than the staining in other liver cells. More neoplastic cells had high BzDH than high AcDH activity. Only BzDH-NADP was localized predominantly to the carcinoma.

Aldehyde Dehydrogenase↗

Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research.

In 1977 Maltoni and Scarnato were the first to demonstrate that benzene is an experimental carcinogen in rats. With that and other experiments, Maltoni et al have shown that benzene administered by ingestion (stomach tube) or inhalation is a multipotential carcinogen in rats (of two different strains) and mice and produces a variety of tumors, namely: Zymbal gland carcinomas, oral and nasal cavity carcinomas, skin carcinomas, acanthomas, dysplasias and carcinomas of forestomach, mammary malignant tumors, hepatomas, liver angiosarcomas, hemolymphoreticular neoplasias, and pulmonary tumors. The incidence of Zymbal gland carcinomas and carcinomas of the oral and nasal cavities is affected by the length of treatment by inhalation and by the age of animals. However, the available epidemiological and experimental data at present do not provide precise information on the risk of doses around or below 10 ppm. Long-term carcinogenicity bioassays at 50, 25, 10, 5 and 1 ppm may be helpful for scientific risk assessment. In addition, these experiments have shown that toluene, xylene, and ethylbenzene, at high concentrations, cause an increase in the number of total malignant tumors.

Animals↗

Two cases of liver angiosarcoma among polyvinyl chloride (PVC) extruders of an Italian factory producing PVC bags and other containers.

Two cases are reported of liver angiosarcoma occurring among polyvinyl chloride (PVC) extruders from a small Italian factory producing PVC bags and other containers. The possibility that PVC extrusion carries a risk of liver angiosarcoma is important because of the very large number of people working with extruding, manufacturing and handling PVC, as compared with the number of people working in PVC polymerization and/or VC production. In the past, the level of vinyl chloride (VC) concentration in PVC extrusion workplaces has been thought to be "safe".

Hemangiosarcoma↗

Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology.

Until recently, the incidence of benzene carcinogenicity was based only on the association between benzene occupational exposure and human leukemia, with many limited case reports and scanty epidemiological data. Available experimental studies up to 1976 on animals were rare, fragmentary, and inadequate, and had failed to prove the carcinogenic effects of benzenes. However, an integrated project of long-term carcinogenicity bioassays, begun in our laboratory in 1976 and still continuing, has shown that benzene produces a variety of tumors in rats including Zymbal gland carcinomas, carcinomas of the oral cavity, hepatocarcinomas, and possibly mammary carcinomas, lymphoreticular neoplasias, and other malignancies. Some of the tumors caused by benzene are uncommon or unusual in the breed of rats studied. Therefore benzene must be considered, under the studied experimental conditions, a strong multipotential carcinogen. The need for more experimental research is emphasized, particularly to assess the carcinogenic effects of low doses. Also recommended are more comprehensive epidemiological investigations, extended to all types of malignancies, and the application of adequate measures for primary prevention.

Animals↗

Vinyl chloride-induced hepatic lesions in man and rodents. A comparison.

Histologic sequences in the liver of rodents exposed by inhalation to gaseous vinyl chloride were compared to the lesions in man exposed to the same agent, mainly in vinyl chloride polymerization plants. An identical sequence, starting with circumscribed proliferation of hepatocytes, soon followed by proliferation of a variety of sinusoidal cells and frequently associated with sinusoidal dilatation, progresses to intralobular and more frequently to trabecular angiosarcoma. Predominantly in young animals and rarely in man, hepatocellular carcinoma develops, but never cirrhosis. The sequence represents a dynamic process of competition between proliferating hepatocytes and sinusoidal cells, of hepatocytes with fibroplasia, between perisinusoidal fibrosis and sinusoidal dilatation, and of proliferation of various sinusoidal cells versus angiosarcoma. The great similarity in the evolution in man and rodents, rarely encountered in other experimental models, supports the prediction of human cancer from animal experiments. The precursor nodules differ from the nodules commonly observed in hepatocarcinogenesis by co-proliferation of sinusoidal cells. The differences in the reactions between man and rodents bespeak a strong fibroblastic reactivity in man. Most important, the precursor lesion of mixed hepatocellular and sinusoidal cell proliferation may be of diagnostic value, being superior to conventional hepatic tests in detection of some initial environmental lesions.

Animals↗

Carcinogenicity bioassays of vinyl chloride monomer: a model of risk assessment on an experimental basis.

Data are presented regarding the final results of the Bentivoglio (Bologna) project on long-term carcinogenicity bioassays of vinyl chloride (VC). The experimental project studied the effects of the monomer, administered by different routes, concentrations and schedules of treatment, to animals (near 7000) of different species, strains, sex and age. To our knowledge this is the largest experimental carcinogenicity study performed on a single compound by a single institution. The results indicate that VC is a multipotential carcinogen, affecting a variety of organs and tissues. In the experimental conditions studied, the neoplastic effects of the monomer were also detected at low doses. The experimental and biological factors greatly affect the neoplastic response to VC. Long-term carcinogenicity bioassays are, at present, a unique tool for the identification and quantification of environmental and occupational risks. Precise and highly standardized experimental procedures are needed to obtain data for risk assessment.

Aerosols↗

Results of sputum, cytology among workers exposed to vinyl chloride monomer and to poly(vinyl chloride).

The results of systematic cytological sputum examinations of 3,380 Italian VC-PVC industry workers and of 2,287 workers in other industries at different potential risk and chosen as control groups are reported. The results indicate an increase in cellular abnormalities and dysplasias in the epithelium of the respiratory tract among VC-PVC workers. These data are in line with experimental results showing that VC produces lung tumors in mice and with early epidemiological evidence among exposed workers.

Humans↗

Recent findings on the carcinogenicity of chlorinated olefins.

Data are presented on factors affecting the carcinogenic effects of chlorinated olefins, such as molecular structure, concentration, length of treatment, route of administration and animal species, strain, sex, and age. The observations are based upon carcinogenicity experimental bioassays of vinyl chloride and vinylidene chloride. Early results, which appear to show that some of these factors (particularly species, strain, and sex) act by affecting the metabolism of the tested compounds, are presented, and the need for metabolic characterization of experimental animals in chemical carcinogenesis is stressed.

Age Factors↗

Occupational chemical carcinogenesis: new facts, priorities and perspectives.

There is need for a new active approach to the problem of occupational carcinogenesis. It is no longer acceptable to adopt a "wait and see" attitude since: 1. evidence suggests that cancer is an "ecological" disease; 2. The carcinogenic risk has been increasing as industrialisation increased; 3. Factory workers are the most exposed population and hazards spread from the work-place to the general population as consumer goods and pollution. It is necessary and possible, to identify potential carcinogens before workers and the general population are exposed. That predictive experiments could be done, is exemplified by the history of stilboestrol, bis (chloromethyl) ether, vinyl chloride and chromium pigments, all of which were reported carcinogenic in animal tests before any epidemiological results were available. Unforturnately, these results were received with scepticism because the test methods were thought to be inadequate. It is necessary to develop the future policy of prevention by: 1. establishing a priority for testing compounds already produced and widespread in occurence and those about to be produced on a large scale; 2. establishing experimental models for determining carcinogenic risk, especially rapid screening tests; 3. study of the more important compounds by long-term bioassays. Full details are given of the testing of vinyl chloride monamer and preliminary results are tabulated for tests on styrene, acrylonitrile and vinylidene chloride.

Animals↗