Cancer Chemopreventive Mechanisms of Tea Against Heterocyclic Amine Mutagens from Cooked Meat

Abstract

Cooking meat and fish under normal conditions produces heterocyclic amine mutagens, several of which have been shown to induce colon tumors in experimental animals. In our search for natural dietary components that might protect against these mutagens, it was found that green tea and black tea inhibit the formation of heterocyclic amine-induced colonic aberrant crypt foci (ACF) in the rat. Since ACF are considered to be putative preneoplastic lesions, we examined the inhibitory mechanisms of tea against the heterocyclic amines. In the initial studies using the Salmonella mutagenicity assay, green tea and black tea inhibited according to the concentration of tea leaves during brewing and the time of brewing; a 2-3-min brew of 5% green tea (w/v) was sufficient for >90% antimutagenic activity. N-hydroxylated heterocyclic amines, which are direct-acting mutagens in Salmonella, were inhibited by complete tea beverage and by individual components of tea, such as epigallocatechin-3-gallate (EGCG). Inhibition did not involve enhanced mutagen degradation, and EGCG and other catechins complexed only weakly with the mutagens, suggesting electrophile scavenging as an alternative mechanism. Enzymes that contribute to the metabolic activation of heterocyclic amines, namely microsomal NADPH-cytochrome P450 reductase and N, O-acetyltransferase, were inhibited by tea in vitro. Studies in vivo established that tea also induces cytochromes P450 and Phase II enzymes in a manner consistent with the rapid metabolism and excretion of heterocyclic amines. Collectively, the results indicate that tea possesses anticarcinogenic activity in the colon, and this most likely involves multiple inhibitory mechanisms.

Coffee and tea consumption and cancers of the bladder, colon and rectum

“…However, coffee contains many lipids that tea does not and these may reduce colon cancer risk through an effect on intestinal transit time and bile secretion (Giovannucci, 1998;Boekema et al, 1999). On the converse side and in contrast to the results of this study, tea contains many antioxidants and has been demonstrated in laboratory studies to have anticarcinogenic effects in the colon (Nasani et al, 1998;Dashwood et al, 1999;Xu and Dashwood, 1999).…”

Cancer Prevention by Natural Compounds

“…These compounds are called an``interceptor molecule''. [40][41][42] g) Angiogenesis and anti-angiogenic action: The question of whether preneoplasias or early stage tumors can continue to grow to a large extent is dependent on the availability of nutrients to sustain anabolism. This in turn will require a su‹cient blood supply and because of the generally solid nature of focal lesions, angiogenesis and therefore anti-angiogenic agents may clearly be of importance.…”

“…13); Green tea polyphenols, classiˆed as members of the ‰avonoid group, including epigallocatechin, epicatechin gallate (ECG) and epigallocatechin-3-gallate (EGCG) have been shown to inhibit carcinogenesis in many organs. 41,108,[113][114][115][116] Anti-oxidant activity, apoptotic potentials to carcinogen-initiated and interaction to cell cycle are the mechanism for the inhibitory eŠects. EGCG inhibits AP-1 activity in the epidermis of a transgenic mouse model.…”

Mechanisms of plant polyphenols anti-cancer effects I. Blockade of carcinogenesis initiation

“…Ингибирование метаболической активации ГА, например, за счёт инактивации цитохромов Р450 приводит к снижению уровня мутагенных молекул и антиканцерогенному эффекту. Обнаружено, что таким образом действуют некоторые полифенолы, в частности, катехины чая [23,24]. Ресвератрол с различной эффективностью ингибирует активность цитохромов CYP1A2, CYP1A1 и CYP1B1, с чем связывают его защитное действие против гетероциклических аминов, а также против ароматических аминов, полициклических ароматических углеводородов (ПАУ), генотоксичных катехоловых метаболитов эстрогена [25][26][27].…”