The people of Minas Gerais will probably think twice before savoring chicken with bracken, intensely consumed by the poorer layers of the population from the Ouro Preto region. The reason is the results of studies carried out by researchers from São Paulo and Minas Gerais, who discovered that bracken fern (Pteridium aquilinum), also known as brake fern or eagle fern, favors the proliferation of the human papilloma virus (HPV), which causes bland problems like warts, or much more serious ones, like tumors of the breast, bladder or digestive apparatus. More frequently, HPV is associated with cervical cancer, which by itself represents 10% of the cases of malignant tumors in women in Brazil, and is the second largest cause of cancer world-wide, after breast cancer.
The researchers examined two groups of residents of Ouro Preto and found that men and women who consumed the fern regularly (up to twice a day), in comparison with people who do not eat it, showed 30% more chromosomal abnormalities, which increases the predisposition towards cancer. Nevertheless, not all the people infected with the virus will necessarily develop the disease: the HPV needs other elements, the so-calledco-factors, which facilitate its action. Until recently, there was no food among the main factors – smoking, alcohol, drugs and the contraceptive pill and the number of sexual partners. Research coordinated by Willy Beçak, the scientific director of the Butantan Institute in São Paulo, shows that Pteridium may be a powerful co-factor that opens up the way for the action of the HPV and the formation of tumors.
“In the human organism, besides causing chromosomal abnormalities, bracken acts as a immunosuppressive agent, lowering the capacity of the defense system to resist”, says Beçak. There is no consensus on which chemical compound in bracken acts as an immunosuppressive agent, but it is now held to be certain that the HPV must not be the only virus whose action may be spurred.
Until now, it was also thought that, in human beings, sexual contact was the only form of contagion for the malignant forms of the virus. But studies carried out by the teams from Butantan and the Federal University of São Paulo (Unifesp), in partnership with the University of Oslo, in Norway, suggest another possibility: the HPV may also be transmitted by the blood. Research originally carried out on cattle showed that the BPV (the bovine papilloma virus and which shares a common basic molecular structure with the HPV) lodges itself in the lymphocytes – blood cells that are part of the defense system – a space where it remains latent, before spreading over the body and helping to unleash the process of tumor formation.
The researchers gathered what they judged to be the first evidence that the same process may happen in human beings. They themselves insist: for the time being, it is a strong indication, which calls attention because it would turn fighting the disease into a more complex problem. “Confirmation experiments are fundamental” points out Rita de Cássia Stocco dos Santos, a researcher from Butantan involved in the work. “Should the hypothesis be confirmed, the transmission of the HPV make be regarded as equivalent to the HIV that causes Aids.”
Charles Lindsey, from Unifesp’s Biophysics Department and one of the project’s collaborators, has found an indication that reinforces the hypothesis. In a parallel study, with 30 women treated for HPV infection, 29 had the virus in the blood. It became clear that the virus modifies the genetic material: two women from the group showed at least ten times more chromosomal aberrations than normal. “We observed some completely pulverized chromosomes”, says Lindsey. The situation which is shaping up may be serious, because the tests that are carried out on blood donations or transfusions take into consideration Aids, hepatitis, syphilis and Chagas’s disease, but does not assess the presence of the HPV. “The public health system is not yet prepared to fight this new form of transmitting the virus, if it is confirmed”, says Beçak.
The search for the relationship between the HPV and several kinds of cancer started in the 80’s, following studies in other countries that related bracken consumption to a higher occurrence of tumors in the bladder and digestive apparatus amongst cattle. From then until now, the Butantan team, in partnership with Unifesp and the Federal University of Ouro Preto (Ufop), decided to check whether the situation was also valid for humans. But they had to depend on luck and on finding people who eat the plant.
They succeeded. In Ouro Preto, Pteridium is eaten by poor populations in the form of stews, with meat, or even drunk as a tea. But it is not a habit that is exclusive to the people from Minas Gerais. The Japanese are also consumers of bracken, which in Venezuela and in Scotland goes into cattle feed. According to Rita, Venezuelan researchers found traces of bracken in cows’ milk, in a region where the occurrence of stomach cancer in humans was higher than normal.
One of the merits of the Butantan group was to create an experimental model in cattle and to try to understand the effects of bracken in humans. In Ouro Preto, the researchers studied 40 residents, half who consumes bracken and half who did not. A cytogenetic analysis, which assesses the number of chromosomes, mutations and breaks in genetic material, showed that the frequency of anomalies and alterations in the first group was about 30% higher. For that reason, a team from Ufop, in partnership with the Municipal Secretariat for Health, tried to advise the inhabitants of Ouro Preto on the ills caused by Pteridium, in an attempt to change their eating habits.
Having established the relationship between bracken and the HPV, the researchers are now dedicated to the most difficult stage: assessing the new forms of transmission of the virus. The observation of herds of cattle raised a question: how animals that had not had any sexual relations could be contaminated with the BPV? Their sores, which the animals scratch rubbing themselves against each other, and the shared use of syringes in the application of vaccines called attention and threw suspicions on the blood. At the end of the 90’s, the teams confirmed the presence of the BPV in bovine lymphocytes and indicated the possibility of transmission through the blood, as attested in an article published in the Journal of General Virology in 1998.
One year earlier, when making known the initial results at an international conference on the papilloma virus, in Sienna, Italy, the Brazilians were contacted by researchers from the University of Oslo, who were looking for help to solve a problem: 56 patients attended to at the university hospital showed cervical cancer, after having been completely cured, five years before, from breast cancer. In none of the cases had there been metastasis, spreading the tumor to other tissues, but cancer had reappeared in other parts of the body. The team from Butantan analyzed blood samples from the women and found the presence of HPV in the lymphocytes. Amongst the more than 100 kinds of virus, those that most infected these patients were the HPV-16 and the HPV-18, linked to breast and cervical tumors.
“The blood was acting as a means of transport for the HPV to other parts of the body. When the virus found the ideal conditions, it generated a new kind of cancer, even after a certain time”, explains Beçak. “It is the first evidence that, in humans, the situation is similar to the one to be seen in animals”. For Lindsey, the results, albeit preliminary, are causing a revision in medical knowledge on the virus and may spawn concrete benefits for society: “If and when it is incorporated into the routine exams, the test that indicates the presence of the HPV in the lymphocytes may make the diagnosis of tumors simpler and less invasive”.
The researchers admit the need for seeking more evidence that confirms transmission by the blood, not least because the studies in human beings are more complicated than in animals. One is thing is sure: the confirmation of this thesis can only come from joining various items of evidence that will validate the experimental results. It was not by chance that the international scientific community received the results of this research with incredulity, when they were presented at the International Papillomavirus Conference in Spain, in 2000.
The researchers intend to expand the studies carried out in Ouro Preto and to assess women who eat bracken in pregnancy, in order to find out whether chromosomal alterations are produced in their babies. The proposal will make it possible to cross data obtained in the two studies – one of Pteridium and the other of the blood – and, if the hypothesis of a transfer is confirmed, it will be one more indication that the transmission of the HPV in humans can take place through the blood, since mother and child communicate through the placenta. They are also taking into consideration studies by groups from the University of Baltimore (United States), the University of Geneva (Switzerland) and from the University of Thailand , which are discussing the possibility of the DNA of the virus being transported by the blood plasma (and not by the lymphocytes).
Internationally, efforts are converging on the production of a vaccine capable of fighting the HPV. In Brazil, the project for arriving at 2 HPV DNA vaccines, one preventive and the other therapeutic, is gathering together teams from Butantan, the University of São Paulo (USP), from Unifesp and from the Ludwig Institute for Cancer Research, in collaboration with the University of Glasgow, in Scotland, while other groups, mainly in the United States, are working on an antigen vaccine, which stimulates the production of antibodies.
Integrated Studies about the Possible Synergism between the Papillomavirus andCo-factors and Oncogenes, Cytogenetic and Molecular Studies (nº 98/11819-9); Modality Regular assistance line to research;
Coordinator Willy Beçak – Butantan Institute; Investment R$ 315,886.78