scispace - formally typeset
Search or ask a question

Showing papers on "Carcinogenesis published in 1973"


Journal ArticleDOI
TL;DR: It is suggested that all cells possess multiple structural genes capable of coding for transforming factors which can release the cell from its normal constraints on growth.
Abstract: A general hypothesis of carcinogenesis is proposed consisting of the following features: (1) It is suggested that all cells possess multiple structural genes (Tr) capable of coding for transforming factors which can release the cell from its normal constraints on growth. (2) In adult cells they are suppressed by diploid pairs of regulatory genes and some of the transforming genes are tissue specific. (3) The Tr loci are temporarily activated at some stage of embryogenesis and possibly during some stage of the cell cycle in adult cells. (4) Spontaneous tumors, or tumors induced by chemicals or radiation, arise as the result of a double mutation of any set of regulatory genes releasing the suppression of the corresponding Tr genes and leading to transformation of the cell. (5) Autosomal dominant hereditary tumors, such as retinoblastoma, are the result of germ-line inheritance of one inactive regulatory gene. Subsequent somatic mutation of the other regulatory gene leads to tumor formation. (6) The Philadelphia chromosome produces inactivation of one regulatory gene by position effect. A somatic mutation of the other leads to chronic myelogenous leukemia. (7) Oncogenic viruses evolved by the extraction of host Tr genes with their conversion to viral transforming genes. As a result, in addition to the above mechanisms, tumors may also be produced by the reintroduction of these genes into susceptible host cells.

450 citations


Book ChapterDOI
TL;DR: This chapter focuses on the degree of involvement of immune mechanisms in modifying tumor formation and growth during chemical carcinogenesis.
Abstract: Publisher Summary This chapter focuses on the degree of involvement of immune mechanisms in modifying tumor formation and growth during chemical carcinogenesis. During the past two decades, the concept that tumors express antigens against which the host is capable of evoking an immune response has been firmly established. The validity of these studies, as well as comparable findings with MC-induced rat sarcomas (Baldwin, 1955), was critically analyzed by Prehn and Main (1957) who conclusively showed that the induction of immunity to transplanted sarcoma grafts was a tumor-specific phenomenon because immunized mice could still accept skin grafts from the tumor donor, precluding the involvement of an alloantigenic immune response. Evidence shows that tumor rejection antigens are specific and permanent, or quasi-permanent, characteristics of cells transformed by chemical carcinogens. Chemically induced tumors also express antigens normally present in embryonic, but not adult, tissue that may be viewed as the products of dedifferentiation processes induced by the carcinogen, and concurrently there is frequently a deletion of normal tissue antigens. The immunological responses to neoantigens expressed on preneoplastic and neoplastic cells can influence, either positively or negatively, the course of chemical carcinogenesis.

213 citations


Journal ArticleDOI
TL;DR: The results demonstrated a highly significant and predictable association between the expression of complete infectious virus or the viral group-specific (gs) antigen in spleens of young mice and tumorigenesis later in life.
Abstract: We analyzed the relationship of genetic factors determining the expression of endogenous type-C RNA tumor viruses and other host-gene markers to tumorigenesis. A hybridization experiment was performed with mice of strains AKR/J and C57L, the first filial (F1) generation hybrids, the second filial (F2) generation hybrids, and the backcrosses to the two parental strains. The results demonstrated a highly significant and predictable association between the expression of complete infectious virus or the viral group-specific (gs) antigen in spleens of young mice and tumorigenesis later in life. Most of the tumors were thymic leukemia and reticulum sarcoma, but other mesenchymal, as well as epithelial, tumors were also observed. Tumors occurred preferentially in gs-antigen- or virus-positive mice of all crosses; in the C57L-backcross and F2 mice segregating for gs-antigen and virus expression, a few gs-antigen-negative mice developed reticulum cell sarcomas. At the time of their occurrence, the mice were all gs-antigen-positive, and most had virus as well. A minor effect of the major histocompatibility locus, H-2, on leukemogenesis was found in the F2 mice. Several tumor types were also found that we have never observed in the two parental strains. Our data provide the most direct biological evidence in favor of the viral oncogene theory. Thus, from the presence or absence of expression in early life of splenic gs antigen or virus, we can predict whether or not a tumor is likely to develop later in life. These findings suggest that the genome of endogenous type-C RNA viruses is the major determinant for tumorigenesis although they provide no clues about the factors responsible for the various histological types.

77 citations


Journal ArticleDOI
14 Feb 1973-Nature
TL;DR: It would be interesting to know if cells as they normally exist in tissues and organs repair DNA in response to these damaging agents, to help relate findings in cultured cells to processes like neoplasia and cell death which have been more extensively studied in the intact animal.
Abstract: RECENTLY, increasing attention has been focused on the role of repair mechanisms in carcinogenesis and cell survival1-7. During the past decade many investigators have demonstrated DNA repair after damage with ultraviolet radiation in cultured mammalian cells2,8,9. Repair is now known to occur after damage with both carcinogenic and non-carcinogenic alkylating agents in similar systems1,4–6,10–14. The molecular events involved in DNA repair in mammalian cells have not yet been completely clarified and most probably are best approached in culture. Nevertheless, it would be interesting to know if cells as they normally exist in tissues and organs repair DNA in response to these damaging agents. Such data should help relate findings in cultured cells to processes like neoplasia and cell death which have been more extensively studied in the intact animal. The data might be especially useful in clarifying conflicting or apparently conflicting findings on the role of repair mechanisms in carcino-genesis2,3,10,14–19.

46 citations


Journal Article
TL;DR: Radioautograms of intact ultraviolet (UV)-irradiated epidermis from a patient with xeroderma pigmentosum showed no detectable abnormality in UV-induced thymidine- 3 H incorporation, suggesting that some mechanism other than enhancement of UV carcinogenesis by defective DNA repair may be responsible for skin tumor formation in this patient.
Abstract: Summary Radioautograms of intact ultraviolet (UV)-irradiated epidermis from a patient with xeroderma pigmentosum showed no detectable abnormality in UV-induced thymidine- 3 H incorporation. This result is consistent with findings in this patient9s UV-irradiated skin fibroblasts and lymphocytes and contrasts with findings in cells from typical xeroderma pigmentosum patients, all of which exhibit an impaired ability to repair UV-damaged DNA. The development of numerous tumors in the presence of apparently normal DNA repair suggests that some mechanism other than enhancement of UV carcinogenesis by defective DNA repair may be responsible for skin tumor formation in this patient and perhaps in all patients with xeroderma pigmentosum.

32 citations


Journal ArticleDOI
TL;DR: A special,class of "zytt~p]nsm~c DNA (eDNA = comrnuniezIion DNA I l l ) is for, and in some animal ceil !

16 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the presence of the sarcoma gene in cells is an essential but not sufficient condition of tumorigenesis, and phenotypic reversion after in vivo inoculation or long term in vitro cultivation.
Abstract: Tumorigenic and nontumorigenic mutants induced by a single 5'-bromodeoxyuridine (BrdU) treatment of a nonproducer (NP) tumorigenic cell line were isolated and characterized. Among the cloned derivatives were examples of virus-free and sarcoma virus-producing cell lines. Oncogenicity did not correlate with production of virus or ease of rescue of the sarcoma genome. All lines, including nononcogenic derivatives, retained the sarcoma genome. Phenotypic reversion of some cell mutants was observed after in vivo inoculation or long term in vitro cultivation. The M-50T cell line, obtained from a tumor induced by M-50 cells, had a sarcoma genome rescuable by direct superinfection; this was only achieved with parental M-50 cells by a cell fusion rescue technique. The M-43-2T cell, obtained from a single small static tumor induced by otherwise nononcogenic M-43-2 cells, shed sarcoma virus and became tumorigenic. M-58-4-48 became tumorigenic after passage 48 of the M-58-4 line, which was originally nontumorigenic. These observations of phenotypic reversion demonstrate that the presence of the sarcoma gene in cells is an essential but not sufficient condition of tumorigenesis.

14 citations



Journal ArticleDOI
Chung Wu1
TL;DR: A reversion of some of the regulatory apparatus in the cancer cell to that in the perinatal stage of development has taken place, and this reversion is considered an essential mechanism in carcinogenesis.
Abstract: Results on enzyme induction in rat liver and kidney tumors have shown a striking resemblance between the tumors and the perinatal liver and kidney, on the one hand, and a sharp contrast between the tumors and the adult liver and kidney, on the other. Studies on isozyme distribution give similar results. Abnormalities in the responsiveness of enzymes to metabolic modulations and in the induction-repression of isozymes reflect aberrations in the regulatory genes of the tumors. Since the liver and kidney tumors have originated from the adult liver and kidney, respectively, but show biochemical properties akin to those of the perinatal liver and kidney, it seems that during oncogenesis certain regulatory genes must have been so altered that the cell reacquires the control mechanisms prevailing in an early period of the life of the organism. Hence, a reversion of some of the regulatory apparatus in the cancer cell to that in the perinatal stage of development has taken place. This reversion is considered an essential mechanism in carcinogenesis.

8 citations


Journal ArticleDOI
TL;DR: Studies using labeled precursors of DNA and RNA indicate that colonic neoplasia begins on the surface of the bowel, when normally senescent cells of the epithelium resume mitosis in response to some exogenous stimulus.
Abstract: Studies using labeled precursors of DNA and RNA indicate that colonic neoplasia begins on the surface of the bowel, when normally senescent cells of the epithelium resume mitosis in response to some exogenous stimulus (eg, something ingested or its metabolic products) The morphology of the tumor is probably determined by the number of cells originally involved Evidence for this concept of colonic carcinogenesis is detailed

7 citations


Journal ArticleDOI
TL;DR: Combined intramuscular inoculation of histone and virus was shown to enhance the carcinogenesis markedly: it inhibited spontaneous regression of tumors, produced progressive growth of tumors followed by death of mice, shortened the latent period of tumor formation, produced metastases in surviving animals.
Abstract: The effect of total histone on oncogenicity of Moloney murine sarcoma virus was studied. Combined intramuscular inoculation of histone and virus was shown to enhance the carcinogenesis markedly: it inhibited spontaneous regression of tumors, produced progressive growth of tumors followed by death of mice, shortened the latent period of tumor formation, produced metastases in surviving animals. A topical effect of histone is suggested, even though it is not excluded that formation of metastases may be associated with its immunodepressive effect.