Immune-hormonal imbalance in chemical cancerogenesis

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Abstract

The present article deals with experimental and clinical aspects of immuno-hormonal interactions in chemical carcinogenesis i.e., formation of DNA-adducts with chemical carcinogens as a trigger of tumor initiation; synthesis of specific antibodies as markers of human exposure to environmental carcinogens; immunomodulation of chemical carcinogenesis by the specific antibodies in experimental studies; interactions of antibodies against environmental carcinogens with endogenous steroid hormones in human carcinogenesis; immunological interference and inversion of immuno-hormonal interactions by the action of antibodies against environmental carcinogens; immune stimulation of tumor progression in cancer patients. It is shown that antibodies specific to estradiol and progesterone participate in regulation of serum estradiol and progesterone levels in healthy women. Excessive production of antibodies against benzo[a]pyrene is associated with impaired physiological balance between the levels of antibodies to estradiol and progesterone, thus causing disturbed physiological balance between serum estradiol and progesterone. Immuno-hormonal imbalance promotes tumor initiation, its growth and progression. The new approaches to the personalized cancer immunoprediction and immune prevention are discussed. Coordinated synthesis of antibodies against benzo[a]pyrene and estradiol seems to reflect production of DNA-adducts with genotoxic metabolic effects of these compounds manifesting as synergistic carcinogenic effects upon the target cells. Hence, simultaneously increased levels of serum antibodies against benzo[a]pyrene and estradiol in healthy people may be considered an immunological marker of high oncological risk and an reason to use of new immunoprotective tools against polycyclic aromatic hydrocarbons and phytoestrogens. However, ability of these antibodies to raise the blood serum levels of environmental carcinogens and endogenous estradiol, as shown in vitro and in vivo, excludes the opportunity for active cancer immune prevention. Usage of anticarcinogen vaccines aimed for induction of protective secretory antibodies is likely to further increase high levels of procarcinogenic serum antibodies against benzo[a]pyrene and estradiol, followed by additional enhancement of immuno-hormonal imbalance and promotion of carcinogenesis. Development of probiotics transduced with genes encoding human antibodies against environmental carcinogens may present an alternative approach to cancer immune prevention. The antibodies produced by such probiotics would bind appropriate carcinogens and prevent their invasion into the organism, thus inhibiting emergence of DNA-adducts and suppressing synthesis of specific autoantibodies that may promote carcinogenesis. The aim is to substantiate the concept of immuno-hormonal imbalance for the carcinogen-induced hormone-dependent tumors.

About the authors

Andrew N. Glushkov

Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry, Siberian Branch of Russian Academy of Sciences

Author for correspondence.
Email: stellamun@yandex.ru
ORCID iD: 0000-0002-8560-6719

PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Immunogenetics

Russian Federation, 650065, Kemerovo, Leningradsky ave., 10

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Supplementary files

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1. JATS XML
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2. Figure 1. Frequency (%) of revealing immunological phenotypes (A, protective; B and C, compensatory, D, procarcinogenic) in healthy women and breast cancer patients [6]

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3. Figure 2. Individual blood serum ratios Pg/Es in healthy women with different immunological phenotypes (A, protectiv; B and C, compensatory; D, procancerogenic) and breast cancer patients (BCP) [7]

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4. Figure 3. Correlations between blood serum Es (A) and Pg (B) concentrations and IgA-Es and IgA-Pg levels in healthy women with low (1) and high (2) IgA-Bp levels [43]

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5. Figure 4. Frequency (%) of high individual IgA-Es/IgA-Pg ratio in breast cancer patients with I and II-IV tumor stages according to ER/PR status

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