Chlorophyll Cancer Protection Study Questions Mice Research Model

CORVALLIS, Ore.Oregon State University (OSU) researchers have discovered chlorophyll in green vegetables can help protect against modest carcinogen exposure levels commonly found in the environment. The downside is chlorophyll increased the number of tumors when carcinogens were at a high exposure levels. Results from the study, which was supported by the National Institutes of Health (NIH), were published in the journal Food and Chemical Toxicology (2012 Feb.;50(2):341-352).

While their earlier studies found positive results with chlorophyll in both mice and trout, the scientists used 12,360 rainbow trout as laboratory models in this study, explaining using rodents is much more expensive, which requires the use of fewer specimens and higher carcinogen exposures. The design of this study featured a dosedose matrix to examine chlorophyll-mediated effects on carcinogen-induced DNA adduct formation (biomarker of exposure and potential cancer development), tumor incidence, tumor multiplicity and changes in gene regulation in the trout. Researchers administered dietary chlorophyll (0 to 4000 ppm) and carcinogen (0 to 25 ppm  of DBC) for up to four weeks.

They found the carcinogen dose-dependently changed gene expression in the fish that were  fixed by the chlorophyll; there were no changes when chlorophyll was given without the carcinogen. WHen given to animals also exposed to the carcinogen, the chlorophyll reduced tumor multiplicity and incidence that had risen due to carcinogenic exposure. However, when carcinogenic exposure was at high levels, chlorophyll failed to inhibit multiplicity and incidence. The researchers noted, " This finding questions the human relevance of chemoprevention studies carried out at high carcinogen doses that are not proven to lie within a linear, or at least monotonic, endpoint doseresponse range."

Tammie McQuistan, one of the researchers, said theres considerable evidence in epidemiologic and other clinical studies with humans that chlorophyll and its derivative, chlorophyllin, can protect against cancer. This study, like others before it, found that chlorophyll can reduce tumors, up to a point, she said. But at very high doses of the same carcinogen, chlorophyll actually made the problem worse. This questions the value of an approach often used in studying cancer-causing compounds.

The researchers explained traditional research involving small numbers of animals fed very high doses of a carcinogen might conclude that chlorophyll has the potential to increase human cancer risk. However, this current study, combined with other evidence, found a more refined and telling result. They noted the results showed the protective mechanism of chlorophyll is fairly simple it just binds with and sequesters carcinogens within the gastrointestinal tract until the dangerous chemicals are eliminated from the body.

The central assumption of such experiments is that intervention effects at high carcinogen dose will apply equally at lower carcinogen doses, the researchers wrote. Contrary to the usual assumption, the outcomes in the major target organ were strikingly dependent on carcinogen dose.