Proliferacja peroksysomow a proces hepatokancerogenezy

• Autorzy: Palut D.
• Języki publikacji: PL

Abstrakty

PL

W artykule przedstawiono aktualny stan wiedzy na temat mechanizmów odpowiedzialnych za rakotwórcze działanie substancji chemicznych z grupy proliferatorów peroksysomów (PPs), różnic gatunkowych we wrażliwości oraz omówiono poglądy dotyczące oceny ryzyka dla ludzi wynikającego z oddziaływania PPs rozpatrywanych jako niegenotoksyczne hepatokancerogeny i/lub promotory raka wątroby.

EN

Peroxisome proliferators are diverse group of chemicals which are regarded as rodent hepatocarcinogens and/or- liver tumor promoters. These compounds when administered to rats and mice produce a dramatic increase in the size and number of hepatic peroxisomes and increase in activities of enzymes involved in beta-oxidation of fatty acids. Peroxisome proliferation is acompanied by hepatocyte proliferation and liver growth. The steroid hormone receptors superfamily have been identified that can be activated by peroxisome proliferators and are called Peroxisome Proliferator Activated Receptors (PPARs). It is therefore suggests that PPARs mediate the pleiotropic effects of peroxisome proliferators including enzyme induction, peroxisome proliferation, cell proliferation and hepatocarcinogenesis. Although the correlation of peroxisome proliferation and hepatocarcinogenesis is striking, the mechanism(s) by which this class of chemicals induce tumor is still understood; however several other hypothesis have been advanced. One is based on knowledge that hydrogen peroxide is produced during the increase in peroxisomal fatty acid oxidation. An excess of hydrogen peroxide can lead to oxidative stress (generation of reactive oxyden species), DNA damage and possibly to tumor initiation. In rodents, an alternative mechanism is the promotion of spontaneously initiated lesions by sustained cell proliferation. Thirdly, it is conceivable that sustained growth stimulation may be sufficient for tumor formation. Marked species differences are apparent in response to peroxisome proliferators. Rats an mice are extremely responsive species, and hamsters show an intermediate response, while guinea pigs, monkeys and humans appear to be relatively non-responsive. In the light of these data it seems likely that risk to humans from peroxisome proliferators may be overestimated. However, peroxiome proliferators have shown to produce the other effects such as the suppression of hepatocyte apoptosis which could be an important factor in their hepatocarcinogenic response.

Słowa kluczowe

PL

dzialanie rakotworcze; nowotwory; choroby czlowieka; ryzyko zachorowan; proliferatory; substancje chemiczne; peroksysomy; proliferacja

EN

carcinogenic activity; cancer; human disease; disease risk; chemical substance; peroxisome; proliferation

• Wydawca: -
• Czasopismo: Roczniki Państwowego Zakładu Higieny
• Rocznik: 1997
• Tom: 48
• Numer: 1
• Opis fizyczny: s.1-11,tab.,bibliogr.

Twórcy

autor

Palut D.

• Panstwowy Zaklad Higieny, 00-791 Warszawa, ul. Chocimska 24