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Editorial

Preneoplastic foci in mice fed diethyl 1, 4-dihydro, 1, 4,
Preneoplastic foci in mice fed diethyl 1, 4-dihydro, 1, 4,
6-trimethyl 3, 5-pyridine decarboxylate are resistant to
6-trimethyl 3, 5-pyridine decarboxylate are resistant to
protoporphyrin accumulation
protoporphyrin accumulation

1
Samuel W. French , M. Waheed Roomi 2
1 Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
2 Dr. Rath Research Institute, Santa Clara, CA 95050, USA

Address for correspondence:
Dr. Samuel W. French, Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA. E-mail: sfrench@labiomed.org
Received: 01-02-2015, Accepted: 23-03-2015

It has been shown that preneoplastic liver cell foci and hepatic complete standard Tekland test diet ad libitum (Tekland,
nodules generated by thioacetamide (TAA) in drug-primed Madison, WI, USA) with 0.1% DDC or 2.5% GF for 1 year and
mice, which were first fed diethyl 1, 4-dihydro, 1, 4, 6-trimethyl then sacrificed. Control mice were fed the basal diet without
3, 5-pyridine decarboxylate (DDC) or griseofulvin (GF) for DDC. As soon as the mice were killed, their liver was removed.
5 months were resistant to protoporphyrin accumulation. Portions of the liver were fixed in formalin and embedded in
[1]
DDC or GF are potent porphyrinogenic drugs and accumulate paraffin for light microscopic analysis by hematoxylin-eosin
protoporphyrin in the mouse liver. Although DDC or GF are and gamma glutamyl transpeptidase (GGT) was accessed
withdrawn for 1 month, when treated with TAA, the nodules by histochemistry. Figure 1 illustrates an HN from a mouse
formed on the 5th or 7th day of treatment were devoid of fed DDC for 1 year. The tumor is devoid of protoporphyrin
protoporphyrin deposits. Feeding DDC or GF for 8 months and is surrounded by normal liver parenchyma filled with
induced liver tumors which were devoid of protoporphyrin protoporphyrin deposits. Figure 2 shows hyperplastic foci
deposits. In contrast, the surrounding liver tissue contained stained red for GGT, a marker for HN, showing that the
numerous protoporphyrin deposits. This could be attributed precursor lesion is devoid of protoporphyrin deposits. HN
to the decreased activity of delta-aminolevulinate synthase, or foci are generated during the process of liver cancer
the first rate-limiting enzyme in protoporphyrin synthesis. development in response to chemical carcinogens or dietary
Furthermore, there could be an increased activity of
ferrochelatase, which catalyzes the incorporation of iron into
protoporphyrin, and increased activity of heme oxygenase,
the last enzyme in porphyrin degradation. Protoporphyrin
deposits were found in the normal liver parenchyma, but
not in the hyperplastic nodules (HNs) or hepatocellular
carcinomas formed in mice fed GF or DDC for 5-12 months. [2-4]
C3H male mice, aged 4 weeks (Harlan, Sprague-Dawley, San
Diego, CA, USA), were fed a protein-rich 25% semisynthetic

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Figure 1: Liver from a mouse fed diethyl 1, 4-dihydro, 1, 4, 6-trimethyl 3, 5-pyridine
DOI:
decarboxylate for 1 year (×57). Note the hyperplastic nodule is devoid of brown
10.4103/2394-5079.155984 protoporphyrin pigment, whereas the surrounding normal liver parenchyma is
fi lled with protoporphyrin deposits

50 Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015