Jill C. Pelling

Tumor cell surface β1–6 branched oligosaccharides and lung metastasis

NIH3T3 cells transfected with an activated Ha-ras oncogene were treated with L-PHA, the leukoagglutinin from red kidney beans. Cell lines resistant to L-PHA-mediated cytotoxicity were isolated and found to contain reduced levels of L-PHA-binding oligosaccharides. The levels of N-acetylglucosaminyltransferase V, the enzyme responsible for the initiation of theβ1–6 branch, were reduced in L-PHA-resistant cells. Tumorigenicity in nude mice was unchanged by the change in oligosaccharide expression, but the ability to form lung tumors after intravenous injection was significantly reduced. These results demonstrate that the ability of NIH3T3 cells transfected with an activated Ha-ras oncogene to form lung tumors after intravenous injection into nude mice is reduced in all six L-PHA selected cell lines containing a reduction inβ1–6 branched Asn-linked oligosaccharides.

The Influence of Dietary Selenium on Colon, Pancreas, and Skin Tumorigenesis

The influence of dietary selenium on experimental carcinogenesis has been extensively investigated in the mammary glands of mice and rats (reviewed by Medina 1986). Most studies on cancer at this site have consistently reported inhibition of mammary carcinogenesis by a number of agents. Recent investigations of dietary selenium’s effects on mammary tumorigenesis were described in the preceding chapter by C. Ip.

Altered Expression of Oncogenes in Mouse Epidermis Following Exposure to Benzo(A)Pyrene Diol Epoxides

There now exists a great deal of evidence which indicates that all normal eukaryotic cells contain endogenous, highly-conserved DNA sequences known as proto-oncogenes (1). The normal functions of these cellular oncogenes are not yet known, although it has been hypothesized that they may be important in cellular differentiation, fetal development and control of cell proliferation (2–4). Since a significant proportion of human cancers are presumed to be the result of exposure to environmental chemicals, extensive research efforts have focused on determining the effects of chemical carcinogens and tumor promoting agents on the expression of these c-onc sequences. Studies by Barbacid and coworkers using the rat mammary carcinoma model have shown that the Ha-ras oncogene is activated in rat mammary carcinomas induced by N-methylnitrosourea (5). Sequencing of the activated rat c-Ha-ras oncogene in individual mammary adenocarcinomas indicated that the rat proto-oncogene had undergone a point mutation in the 12th codon, resulting in a glycine-for-valine substitution in the ras P21 protein product. In similar studies, Balmain and Pragnell employed the two stage model of initiation and promotion in mouse skin to demonstrate that a percentage of papillomas and carcinomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) and promotion with 12-0-tetradecanoyl phorbol-13acetate (TPA) contained elevated levels of Ha-ras transcripts compared with normal mouse epidermis. Furthermore, DNA from papillomas and squamous cell carcinomas caused morphological transformation of NIH/3T3 cells in vitro (6,7). Southern blot hybridization studies demonstrated that the transforming properties of the DNA were due to transfection of an activated cellular Ha-ras oncogene.