Chemical carcinogenesis studies

Difluoronaphthalene [315-52-6] is prepared from 4-fluoro-l-naphthylarnine by the Balz-Schiemann reaction. 1,4-Difluoronaphthalene is used in chemical carcinogenesis studies as a synthon for highly condensed difluoro—polycycHc aromatic hydrocarbons (273). 

Thorgeirsson UP, Dalgard DW, Reeves J, et al Tumor incidence in a chemical carcinogenesis study of nonhuman primates. Reg Toxicol Pharmacol 19 130-151, 1994... 

Adamson RH, Sieber SM Chemical Carcinogenesis Studies in Nonhuman Primates. EPA-600/9-83-008. NTIS PB 83-220137, 1983... 

Huff J, Haseman J, Rail D. Scientific concepts, value and significance of chemical carcinogenesis studies. Ann Rev Pharmacol Toxicol 1991 31 621-52. 

Massey TE The 1995 Pharmacological Society of Canada Merck Frosst award - Cellular and molecular targets, in pulmonary chemical carcinogenesis - studies with aflatoxin Bj. Can J Physiol Pharmacol 1996 74 621-628. 

As to the debate on the use of estimated MTD in chronic toxicity/carcinogenicity studies, recent information may be found in two letters by Abel son (26) and McConnell (27). Abel son suggests that the public has been misinformed through "a media barrage" by the results of chemical carcinogenesis studies in animals, particularly in rodents (26). One of the criticisms from Abelson was the use of "massive doses" (i.e., MTD) which, in his opinion, "vastly exceed those to which humans are likely to be exposed" (26). McConnell... 

Similar results were obtained by feeding naturally occurring CLA in fact, the CLA preparation used to date for chemical carcinogenesis studies consists of a... 

Some years ago Rose was the first to draw attention to the possible cytotoxic and carcinogenic role of arylnitrenes. Recently, photolysis of 2-azidofluorene in situ has been used as a probe for chemical carcinogenesis in mammalian cell cultures. It has the advantage of bypassing metabolic activation. Clearly, one can expect to see an increase in the use of azides, which are structurally related to known carcinogens, as specific photoaffinity labels in chemical carcinogenesis studies. 

Some of the most convincing evidence for the chemoprevention of cancer by retinoids comes from chemical carcinogenesis studies of the mammary gland. The earliest study to report an inhibition of mammary carcinogenesis was that of Moon et al. (1976), who found a 52% reduction in the incidence of mammary cancer in rats treated with DMBA and 2.5 mg of retinyl acetate per day, compared to that of animals receiving DMBA and a placebo diet. A previous report... 

Experimental animal studies have played a key role in the understanding of the mechanisms of chemical carcinogenesis. The duration of development of a cancer in humans may be several decades, and the development probably includes several steps. Furthermore, individual susceptibility is also important for the disease. Therefore, it has been extremely difficult to make the required observations in exposed individuals. 

Our studies on cyclic nitrosamine metabolism are supported by NCI Grants CA-21393, CA23901, and CA12376. This is paper Number 34 in A Study of Chemical Carcinogenesis. ... 

The reaction of metabolically generated polycyclic aromatic diol epoxides with DNA Ua vivo is believed to be an important and critical event in chemical carcinogenesis Cl,2). In recent years, much attention has been devoted to studies of diol epoxide-nucleic acid interactions in aqueous model systems. The most widely studied reactive intermediate is benzo(a)pyrene-7,8-diol-9,10-epoxide (BaPDE), which is the ultimate biologically active metabolite of the well known and ubiquitous environmental pollutant benzo(a)pyrene. There are four different stereoisomers of BaPDE (Figure 1) which are characterized by differences in biological activities, and reactivities with DNA (2-4). In this review, emphasis is placed on studies of reaction mechanisms of BPDE and related compounds with DNA, and the structures of the adducts formed. 

Historically the process of activation has almost exclusively been studied by metabolizing compounds with liver preparations, leading most investigators in chemical carcinogenesis to think that... 

Although aminoacyl-tRNA synthetases are necessary for protein synthesis in all tissues, their importance in chemical carcinogenesis is difficult to assess. Mutation induction by this pathway has been studied extensively (123), yet metabolic activation in a carcinogen-target tissue has not been demonstrated. The only exception is hepatic prolyl-tRNA synthetase activation of N-hydroxy-Trp-P-2 however, hepatic O-acetylation of this substrate also occurs to an appreciable extent (12). Further investigations involving the use of specific enzyme inhibitors would be helpful in addressing this problem. 

Sugimura, T. 1986. Studies on environmental chemical carcinogenesis in Japan. Science 233 312-318. 

Considering the relevance of aza-PAHs in the elucidation of the mechanism of chemical carcinogenesis, our goal was to apply DFT methods to achieve a better understanding of the structural and electronic factors affecting the reactivity of this type of compounds. In this chapter we summarize our recent and ongoing computational studies in this field. 

The K-region -oxirans (63) and (64), of interest in studies of chemical carcinogenesis, have been prepared by cyclization with TDAP of the dialdehydes obtained by oxidative cleavage of the parent hydrocarbons.54... 

Huff JE, McConnell EE, Haseman JK, et al. 1988. Carcinogenesis studies results of 398 experiments on 104 chemicals from the U.S. National Toxicology Program. In Maltoni C., Selikoff I.J., ed. Annals of the New York Academy of Sciences. Living in a Chemical World Occupational and Environmental Significance of Industrial Carcinogens. Vol. 534, New York, NY New York Academy of Sciences, 1 -30. 

Intraperitoneal injection of metallic mercury in rats has produced sarcomas. The sarcomas develop without exception at those sites in direct contact with the metal, suggesting a foreign body reaction rather than chemical carcinogenesis. Mercuric chloride was tested for carcinogenicity in 2-year gavage studies in mice and rats." Three of 49 high-... 

Many experimental obs vations, some of which have predicted human cancer data, have been possible because of organ-specific animal models for chemical carcinogenesis. These models, being similar to thdr human counterparts, strengthen the association of environmental exposures with cancer development, and aid in the extrapolation of carcinogenesis data from animal species to humans. They also provide a valuable resource for studies of pathogenesis, risk-modifying factors, and cancer prevention. 

K., Enomoto, M. Sakabe, H. (1994) Two-year toxicological and carcinogenesis studies of 1, 4-dioxane in F344 rats and BDFl mice. Drinking studies. Proceedings on the Second Asia-Pacific Symposium on Environmental and Occupational Health, Environmental and Occupational Chemical Hazards (2), Kobe University, pp. 193-198... 

Turusov, V.S., Chemeris, GY Parfenov, Y.D. (1985) Pararenal angiosarcoma induced in male mice by 1,2-dimethylhydrazine—a model for studying the role of androgens in chemical carcinogenesis. Carcinogenesis., 6, 325-331... 

Until the mid-1970s, most studies in chemical carcinogenesis were experimental, i.e., suspect materials were placed continuously on the skin or in the diets of laboratory animals who were then observed to see if any neoplasms developed. While such work was invaluable in identifying materials which should be removed from the environment, or otherwise avoided, it did not provide any major understanding of the basis of chemical carcinogenesis. Indeed, many of the dermal tests merely indicated allergic reactions and many of the dietary tests showed that some animals thrived on trace additives. 

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