The use of carcinogen-DNA adduct antisera for quantitation and localization of genomic damage in animal models and the human population.

The use of antibodies to detect chemical carcinogen-induced DNA damage involves quantitative determination and morphological localization utilizing antisera specific for carcinogen-DNA adducts. In recent years a large number of polyclonal and monoclonal antisera have been produced against individual adducts and modified DNAs with addition products varying in structure from ethyl and methyl groups to aromatic amines, polycyclic aromatic hydrocarbons, aflatoxins, and platinum-ammine complexes. The quantitative assays developed through the use of these antisera are able to detect attomole (10(-18) M) adduct concentrations, corresponding to one adduct in 10(8) nucleotides or a few hundreds of modifications per mammalian cell genome. This review focuses on data generated during the past 3 yr utilizing this immunotechnology as a tool to probe mechanisms of carcinogen-DNA interactions in various model systems and in the human population. Areas discussed in depth include quantitative and morphological studies involving detection of 2-acetylaminofluorene-DNA adducts in rat liver, O6-ethyl and O6-methyl deoxyguanosine adducts in rat brain, benzo[a]pyrene-DNA adducts in mouse skin and cis-diamminedichloroplatinum (II)-DNA adducts in peripheral nucleated blood cells of cancer patients.

Antibody stimulation of benzo(a)pyrene carcinogenesis.

Benzo(a)pyrene (BP) was conjugated to horse serum albumin (HSA) and then attached to aldehyde fixed human erythrocytes. These cells were used in a passive hemagglutination test to measure BP antibody. BP antibodies were found to be induced in Swiss mice injected with tumorigenic doses of BP. Of the mice treated with BP, those which developed tumors soonest had the highest levels of BP antibody. This observation suggested that the antibody to BP may stimulate tumor development. When rabbit antibody to BP was injected with BP a significantly increased tumor formation occurred. Active immunization using BP conjugated to a foreign protein also significantly increased tumor formation when the mice were treated with BP. Our findings suggest that the immune response to carcinogens is an important component of the carcinogenic process.

[Detection of 3-OAA containing antigens at early stages of carcinogenesis]. / Vyiavlenie antigenov, soderzhashchikh 3-OAK, na rannikh stadiiakh kantserogeneza

Quantitative and qualitative methods of precipitation rendered it possible to record 3-OAA-antigens and corresponding antibodies in blood and urine preparations from outbred rats receiving hepatocarcinogen DAB.

[Viruses and brain tumors (author's transl)].

This brief review paper deals mainly with oncogenic DNA viruses originally isolated from human patients, i.e., human adenoviruses and human papova JC viruses. Human adenovirus type 12 was first isolated in 1953 in cell cultures derived from the adenoids of infected children. Since then, 32 antigenic types of human adenovirus have been identified. At least eight serotypes (12, 18, 31, 3, 7, 14, 16, and 21) are now known to be capable of producing tumors in newborn rodents. A direct causal relationship between a human adenovirus and malignant transformations in target cells (sensory neuronal precursors) has been definitely established by the development of a medullo-epitheliomatous neoplasm in the brain and spinal cord of an outbred strain of CD rats at as high an incidence as 90%. Intraocular inoculation of adenovirus in newborn rats within one week also has produced typical retinoblastomatous neoplasms. The remarkably uniform histopathologic appearance of all these malignancies in nervous tissue can be attributed to a primitive neuro-epitheliomatous neoplasm derived from sensory microneuron precursors that densely populate both the ventricular zone and the premature sensory retina at the point of virus inoculation. All of these brain and retinal tumors appear to share a common tumor phenotype, as all tumor cells contain cilia with the same morphology (a 9+0 pattern of doublets associated with a pair of centrioles). The production of adenovirus tumor-specific neoantigen (T), an earmark of the viral genome, can be regularly demonstrated by the immunofluorescein microscopic procedure. All transformed cells within both the ventricular zone and the retinal ganglion cell anlage thus appear to continue the production of (T) antigens. These findings lead us to assume that the target cell determinants in adenovirus tumorigenesis may reside in differentiating microneuron precursors ordained for the sensory neuronal complex.