POPs and Human Health

We associate concepts of mutagens and cancer, including child cancer, due to several reasons. Let us discuss the concept of mutagen.

A physical or a chemical agent is defined as a mutagen, if it's impacts may generate mutations in cellular genetic apparatus. Mutations belong to tools of the natural evolution, it is the phenomenon of mutation, that generated so wide diversity of plants and animals on the Earth. Additional mutations among some individual plants or animals guaranteed their preferential survival and facilitated emergence of new species. However, besides biologically beneficial mutations, some other mutations produced defective, non-viable organisms.

Natural causes of death of all living things, in absence of such causes of premature death as chronic diseases or injuries, are mainly represented by two mechanisms: cellular apoptosis or malignant transformation, which manifests itself at the body level as cancer. Development of malignant tumours (or carcinogenesis) would be impossible without involvement of mutagens, which play carcinogenic roles.

In our today's lecture we will focus on chemical mutagens. Mutagens may be categorised into exogenous and endogenous ones. As endogenous mutagens we consider different metabolic products, which form in a human body in physiological or pathological conditions. The range of the most well studied mutagens of the first group includes tyrosine and its derivatives, hormones, etc. Exogenous or environmental mutagens may include chemical compounds, chronic infections, dust, mineral fibres, etc.. Sources of carcinogens may be found among almost all components of the life cycle of a human being.

Therefore, the problem in question may be considered in the following sequence: evolution - environment - cancer. Now, environmental oncology is considered as a specialised branch of medical science.

Incidence of child cancer reaches 1-2%, and the rate remained stable within more than 30 years of observation. From the one hand, so low incidence of child cancer may be perceived as an indication of seemingly favourable situation. However, even preliminary analysis reveals growth of absolute numbers of children with malignant tumours. So called "stability" is a mere result of a fairly stable biological mechanism of destruction of malignant cells by the immune system. This means, that, from the one hand, even minimal impacts of mutagens result in DNA changes, but, from the other hand, the evolution developed mechanisms to prevent premature death from cancer. There is another particular feature of genetically-induced cancer - i.e. long latent periods, which depend on particular impacts and may vary from 2-3 years to 75 years. However, the environment, or, to be more precise - its deterioration - may affect the equilibrium.

The chain of carcinogens - mutagens - child cancer incorporate many additional links, and carcinogenesis starts long before a child's birth. Genetic consequences of impacts of chemical pollutants are comparatively well known. For example, reduction of conceptions was found for wives of workers, exposed to vynylchloride. Girls, whose mothers used some brands of contraceptives for family planning (diethylbestrole), were found to suffer vaginal tumours. Notwithstanding aggressive advertising in favour of use of hormonal contraceptives, scientists still discuss the issue of their safety. Employment of parents at paint-production facilities results in higher incidence of leukosis, brain tumours and Wilms' tumours among their children. Higher leukosis incidence was found for children of parents, who have occupational contacts with diesel oil or work at wood-processing facilities. In the case of transport personnel, benzene was found to be the main occupational mutagen.

The above conclusion is based on findings of animal studies and on particular patterns of development of leukosis cases (mainly myeloid ones) among workers under occupational exposure to benzene. In the case of children of these workers, prevalence of myelopathia disappears and children suffer from lymphoblast leukosis, which is more typical for their age group.

Particles of wood dust contain N-nitrosodiethylamine, classified by specialists as a carcinogen, which causes growing incidence of lymphogranuloma among workers of furniture industry comparatively to control groups. According to information of Russian and foreign researchers, higher risks of malignant tumours for children of smoking parents may be associated with the fact that components of tobacco smoke inhibit DNA reparation, induce mitotic recombination, induce gene conversion and mutations. In this case, it does not matter, whether one or the both parents of a child smoke, because tobacco smoke components act at the stage of foetal development, generate somatic impairments and initiate carcinogenesis.

Many scientists discuss roles of pesticides in cases of liver cancer among residents of rural areas (including children). Food products play a special role among mutagens. These mutagens include infamous natural mixtures of aphlotoxins (produced by Aspergill fungi), which behave as more potent carcinogens (inducing hepatoblastoma) than hepatitis B. Higher incidence of liver cancer cases among African children might be attributed to impacts of these toxins, because many fruit and vegetable products in African countries are contaminated by aphlotoxins.

Potato chips, which are so common and popular among the young now, in some countries (including UK) are prohibited for sale to minors, due to high levels of dangerous carcinogens. In some cases, mutagens generate only higher sensitivity to mutagens in the first generation of descendants, i.e. tumours appear only among descendants of 3rd and 4th generations (from clinical point of view it is considered as a predisposition to cancer).

Analysis of data on some families, when it is possible to trace 3-4 generations, allows to reveal the trend of development of tumours among younger age groups. Some forms of malignant tumours are of hereditary nature and are clearly associated with genetic defects. For example, retinoblastoma is more often registered among several members of a single family, comparatively to other forms of malignant tumours, while Wilms' tumour was found to affect children with defects of 13th chromosome. However, at the contemporary level of development of the medical science we observe some reduction of relative importance of natural selection factors: e.g. decrease of perinatal mortality, levelling of "infection selection" factors. Besides that, accumulation of undesirable mutations in a population is also associated with growing incidence of cancer reconvalescents. Due to these factors, an epidemiological research of child cancer starts from study of a family tree, occupational work records of parents and genetic tests.

Carcinogens often generate irreversible effects (these effects are confirmed by induction of malignant growth after a single contact with carcinogens in animal studies). However, in the case of humans, multiple, repeated contacts with carcinogens are usually necessary to initiate a malignant growth. Impacts of separate doses of carcinogens are of additive and even synergetic nature. In modern megapolices synergy of different carcinogens is often observed. Studies of our Centre also confirm these effects - we identified maximal incidence of lymphoblast leukosis among children of the suburban area (10 cases per 100000 children - the figure exceeds the Oblast averages in 2.5 times).

Environmental effects are usually associated with simultaneous impacts of chemical pollution (emissions of metallurgic facilities) and radiation.

Therefore, identification of links between child cancer and some particular impacts is usually based on published sources and industry-specific regulations and standards. It this case it is especially important to trace proven carcinogens within the range of potential impacts to assess environmental causes of cancer incidence in children's population. The second important approach is based on oncologic monitoring, that is of decisive importance for cancer-prevention actions at the level of population. At the level of individuals, it is very important to remember, that besides activators of pro-oncogens (genes, responsible for malignant transformation), there are naturally occurring substances, which act as inhibitors of carcinogens. These substances act as reparants and antioxidants (they may be found in many food products - e.g. apples, pineapples, green tea, ascorbic acid). Unfortunately enough, the relevant branch of medical science - nutriology - is treated as a mere stepdaughter of the official medical science.